Genetic variation in pattern recognition receptors: Functional consequences and susceptibility to infectious disease

Future Microbiology

Volumn 10, Issue 6, 2015, Pages 989-1008

  Jaeger, Martin ^a   Stappers, Mark H T ^a,b,c   Joosten, Leo A B ^a   Gyssens, Inge C ^a,b,c   Netea, Mihai G ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b CANISIUS WILHELMINA HOSPITAL   (Netherlands)

^c HASSELT UNIVERSITY   (Belgium)

Author keywords

disease susceptibility; genetic variation; infectious disease; pattern recognition; polymorphism; receptors; single nucleotide

Indexed keywords

ABSENT IN MELANOMA 2 LIKE RECEPTOR; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CASPASE RECRUITMENT DOMAIN PROTEIN 4; CD209 ANTIGEN; DECTIN 1; LECTIN RECEPTOR; MANNOSE RECEPTOR; MDA5 PROTEIN; NUCLEOTIDE BINDING OLIGOMERIZATION DOMAIN LIKE RECEPTOR; PATTERN RECOGNITION RECEPTOR; PENTRAXIN 3; RETINOIC ACID INDUCIBLE PROTEIN I; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 10; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 6; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; TOLL LIKE RECEPTOR 9; UNCLASSIFIED DRUG;

GENETIC VARIABILITY; HUMAN; IMMUNE DEFICIENCY; INFECTION; INFECTION SENSITIVITY; INNATE IMMUNITY; PATTERN RECOGNITION; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; COMMUNICABLE DISEASE; GENETIC PREDISPOSITION; GENETICS; IMMUNOLOGY;

COMMUNICABLE DISEASES; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HUMANS; IMMUNITY, INNATE; RECEPTORS, PATTERN RECOGNITION; SIGNAL TRANSDUCTION;

EID: 84930974069     PISSN: 17460913     EISSN: 17460921     Source Type: Journal    
DOI: 10.2217/fmb.15.37     Document Type: Review

References (201)

1. World Health Organization. World Health Statistics 2014. http://apps.who.int/iris/bitstream
2. Sorensen TI, Nielsen GG, Andersen PK, Teasdale TW. Genetic and environmental influences on premature death in adult adoptees. N. Engl. J. Med. 318(12), 727-732 (1988).
3. Buckley RH. Primary immunodeficiency diseases due to defects in lymphocytes. N. Engl. J. Med. 343(18), 1313-1324 (2000).
4. Van De Vosse E, Van Dissel JT, Ottenhoff TH. Genetic deficiencies of innate immune signalling in human infectious disease. Lancet Infect. Dis. 9(11), 688-698 (2009).
5. Janeway CA Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harbor Symp. Quant. Biol. 54(Pt 1), 1-13 (1989).
6. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 449(7164), 819-826 (2007).
7. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 124(4), 783-801 (2006).
8. Popa C, Abdollahi-Roodsaz S, Joosten LA et al. Bartonella quintana lipopolysaccharide is a natural antagonist of Toll-like receptor 4. Infect. Immun. 75(10), 4831-4837 (2007).
9. Hansen JM, Golchin SA, Veyrier FJ et al. N-glycolylated peptidoglycan contributes to the immunogenicity but not pathogenicity of Mycobacterium tuberculosis. J. Infect. Dis. 209(7), 1045-1054 (2014).
10. Coulombe F, Divangahi M, Veyrier F et al. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J. Exp. Med. 206(8), 1709-1716 (2009).
11. Unterholzner L, Keating SE, Baran M et al. IFI16 is an innate immune sensor for intracellular DNA. Nat. Immunol. 11(11), 997-1004 (2010).
12. Feuk L, Carson AR, Scherer SW. Structural variation in the human genome. Nat. Rev. Genet. 7(2), 85-97 (2006).
13. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86(6), 973-983 (1996).
14. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5(10), 987-995 (2004).
15. Kawai T, Akira S. The role of patternrecognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11(5), 373-384 (2010).
16. Ma X, Liu Y, Gowen BB, Graviss EA, Clark AG, Musser JM. Full-exon resequencing reveals Toll-like receptor variants contribute to human susceptibility to tuberculosis disease. PLoS ONE 2(12), e1318 (2007).
17. Johnson CM, Lyle EA, Omueti KO et al. Cutting edge: a common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. J. Immunol. 178(12), 7520-7524 (2007).
18. Wong SH, Gochhait S, Malhotra D et al. Leprosy and the adaptation of human Toll-like receptor 1. PLoS Pathog. 6, e1000979 (2010).
19. Plantinga TS, Johnson MD, Scott WK et al. Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J. Infect. Dis. 205(6), 934-943 (2012).
20. Leoratti FM, Farias L, Alves FP et al. Variants in the Toll-like receptor signaling pathway and clinical outcomes of malaria. J. Infect. Dis. 198(5), 772-780 (2008).
21. Schuring RP, Hamann L, Faber WR et al. Polymorphism N248S in the human Toll-like receptor 1 gene is related to leprosy and leprosy reactions. J. Infect. Dis. 199(12), 1816-1819 (2009).
22. Stappers MH, Thys Y, Oosting M et al. TLR1, TLR2, and TLR6 gene polymorphisms are associated with increased susceptibility to complicated skin and skin structure infections. J. Infect. Dis. 210(2), 311-318 (2014).
23. Kesh S, Mensah NY, Peterlongo P et al. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann. NY Acad. Sci. 1062, 95-103 (2005).
24. Dalgic N, Tekin D, Kayaalti Z et al. Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis. Hum. Immunol. 72(5), 440-445 (2011).
25. Ogus AC, Yoldas B, Ozdemir T et al. The Arg753GLn polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur. Respir. J. 23(2), 219-223 (2004).
26. Schroder NW, Diterich I, Zinke A et al. Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease. J. Immunol. 175(4), 2534-2540 (2005).
27. Kijpittayarit S, Eid AJ, Brown RA, Paya CV, Razonable RR. Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation. Clin. Infect. Dis. 44(10), 1315-1320 (2007).
28. Kang SH, Abdel-Massih RC, Brown RA, Dierkhising RA, Kremers WK, Razonable RR. Homozygosity for the Toll-like receptor 2 R753Q single-nucleotide polymorphism is a risk factor for cytomegalovirus disease after liver transplantation. J. Infect. Dis. 205(4), 639-646 (2012).
29. Etokebe GE, Skjeldal F, Nilsen N et al. Toll-like receptor 2 (P631H) mutant impairs membrane internalization and is a dominant negative allele. Scand. J. Immunol. 71(5), 369-381 (2010).
30. Rosentul DC, Delsing CE, Jaeger M et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front. Microbiol. 5, 483 (2014).
31. Stappers MH, Oosting M, Ioana M et al. Genetic variation in the inhibitory Toll-like receptor 10 influences susceptibility to complicated skin and skin structure infections.. J. Infect. Dis. pii: jiv229 (2015) (Epub ahead of print).
32. Agnese DM, Calvano JE, Hahm SJ et al. Human Toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. J. Infect. Dis. 186(10), 1522-1525 (2002).
33. Lorenz E, Mira JP, Frees KL, Schwartz DA. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch. Intern. Med. 162(9), 1028-1032 (2002).
34. Barber RC, Aragaki CC, Rivera-Chavez FA, Purdue GF, Hunt JL, Horton JW. TLR4 and TNF-alpha polymorphisms are associated with an increased risk for severe sepsis following burn injury. J. Med. Genet. 41(11), 808-813 (2004).
35. Hawn TR, Scholes D, Li SS et al. Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women. PLoS ONE 4(6), e5990 (2009).
36. Rezazadeh M, Hajilooi M, Rafiei A et al. TLR4 polymorphism in Iranian patients with brucellosis. J. Infect. 53(3), 206-210 (2006).
37. Hawn TR, Verbon A, Janer M, Zhao LP, Beutler B, Aderem A. Toll-like receptor 4 polymorphisms are associated with resistance to Legionnaires' disease. Proc. Natl Acad. Sci. USA 102(7), 2487-2489 (2005).
38. Faber J, Henninger N, Finn A, Zenz W, Zepp F, Knuf M. A Toll-like receptor 4 variant is associated with fatal outcome in children with invasive meningococcal disease. Acta Paediatr. 98(3), 548-552 (2009).
39. Faber J, Meyer CU, Gemmer C et al. Human Toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy. Pediatr. Infect. Dis. J. 25(1), 80-81 (2006).
40. Ferwerda B, Kibiki GS, Netea MG, Dolmans WM, Van Der Ven AJ. The Toll-like receptor 4 Asp299Gly variant and tuberculosis susceptibility in HIV-infected patients in Tanzania. AIDS 21(10), 1375-1377 (2007).
41. Najmi N, Kaur G, Sharma SK, Mehra NK. Human Toll-like receptor 4 polymorphisms TLR4 Asp299Gly and Thr399Ile influence susceptibility and severity of pulmonary tuberculosis in the Asian Indian population. Tissue Antigens 76(2), 102-109 (2010).
42. Bochud PY, Sinsimer D, Aderem A et al. Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy. Eur. J. Clin. Microbiol. Infect. Dis. 28(9), 1055-1065 (2009).
43. Bochud PY, Chien JW, Marr KA et al. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 359(17), 1766-1777 (2008).
44. Carvalho A, Pasqualotto AC, Pitzurra L, Romani L, Denning DW, Rodrigues F. Polymorphisms in Toll-like receptor genes and susceptibility to pulmonary aspergillosis. J. Infect. Dis. 197(4), 618-621 (2008).
45. De Boer MG, Jolink H, Halkes CJ et al. Influence of polymorphisms in Innate Immun. genes on susceptibility to invasive aspergillosis after stem cell transplantation. PLoS ONE 6(4), e18403 (2011).
46. Koldehoff M, Beelen DW, Elmaagacli AH. Increased susceptibility for aspergillosis and post-transplant immune deficiency in patients with gene variants of TLR4 after stem cell transplantation. Transpl. Infect. Dis. 15(5), 533-539 (2013).
47. Van Der Graaf CA, Netea MG, Morre SA et al. Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection. Eur. Cytokine Netw. 17(1), 29-34 (2006).
48. Tal G, Mandelberg A, Dalal I et al. Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J. Infect. Dis. 189(11), 2057-2063 (2004).
49. Mockenhaupt FP, Cramer JP, Hamann L et al. Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria. Proc. Natl Acad. Sci. USA 103(1), 177-182 (2006).
50. Mockenhaupt FP, Hamann L, Von Gaertner C et al. Common polymorphisms of Toll-like receptors 4 and 9 are associated with the clinical manifestation of malaria during pregnancy. J. Infect. Dis. 194(2), 184-188 (2006).
51. Hawn TR, Verbon A, Lettinga KD et al. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease. J. Exp. Med. 198(10), 1563-1572 (2003).
52. Lee SO, Brown RA, Razonable RR. Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients. Transpl. Infect. Dis. 15(2), 111-119 (2013).
53. Svensson A, Tunback P, Nordstrom I, Padyukov L, Eriksson K. Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection. J. Gen. Virol. 93(Pt 8), 1717-1724 (2012).
54. Sironi M, Biasin M, Cagliani R et al. A common polymorphism in TLR3 confers natural resistance to HIV-1 infection. J. Immunol. 188(2), 818-823 (2012).
55. Kindberg E, Vene S, Mickiene A, Lundkvist A, Lindquist L, Svensson L. A functional Toll-like receptor 3 gene (TLR3) may be a risk factor for tick-borne encephalitis virus (TBEV) infection. J. Infect. Dis. 203(4), 523-528 (2011).
56. Schott E, Witt H, Neumann K et al. Association of TLR7 single nucleotide polymorphisms with chronic HCV-infection and response to interferon-a-based therapy. J. Viral. Hepat. 15(1), 71-78 (2008).
57. Oh DY, Baumann K, Hamouda O et al. A frequent functional Toll-like receptor 7 polymorphism is associated with accelerated HIV-1 disease progression. AIDS 23(3), 297-307 (2009).
58. Davila S, Hibberd ML, Hari Dass R et al. Genetic association and expression studies indicate a role of Toll-like receptor 8 in pulmonary tuberculosis. PLoS Genet. 4(10), e1000218 (2008).
59. Dalgic N, Tekin D, Kayaalti Z, Cakir E, Soylemezoglu T, Sancar M. Relationship between Toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis. Dis. Markers 31(1), 33-38 (2011).
60. Engin A, Arslan S, Kizildag S et al. Toll-like receptor 8 and 9 polymorphisms in Crimean-Congo hemorrhagic fever. Microbes Infect. 12(12-13), 1071-1078 (2010).
61. Wang CH, Eng HL, Lin KH, Liu HC, Chang CH, Lin TM. Functional polymorphisms of TLR8 are associated with hepatitis C virus infection. Immunology 141(4), 540-548 (2014).
62. Wang CH, Eng HL, Lin KH et al. TLR7 and TLR8 gene variations and susceptibility to hepatitis C virus infection. PLoS ONE 6(10), e26235 (2011).
63. Velez DR, Wejse C, Stryjewski ME et al. Variants in Toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans. Hum. Genet. 127(1), 65-73 (2010).
64. Esposito S, Molteni CG, Zampiero A et al. Role of polymorphisms of Toll-like receptor (TLR) 4, TLR9, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A genes in malaria susceptibility and severity in Burundian children. Malar. J. 11, 196 (2012).
65. Sawian CE, Lourembam SD, Banerjee A, Baruah S. Polymorphisms and expression of TLR4 and 9 in malaria in two ethnic groups of Assam, northeast India. Innate Immun. 19(2), 174-183 (2013).
66. Chuang T, Ulevitch RJ. Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells. Biochim. Biophys. Acta 1518(1-2), 157-161 (2001).
67. Govindaraj RG, Manavalan B, Lee G, Choi S. Molecular modeling-based evaluation of hTLR10 and identification of potential ligands in Toll-like receptor signaling. PLoS ONE 5(9), e12713 (2010).
68. Guan Y, Ranoa DR, Jiang S et al. Human TLRs 10 and 1 share common mechanisms of innate immune sensing but not signaling. J. Immunol. 184(9), 5094-5103 (2010).
69. Laayouni H, Oosting M, Luisi P et al. Convergent evolution in European and Rroma populations reveals pressure exerted by plague on Toll-like receptors. Proc. Natl Acad. Sci. USA 111(7), 2668-2673 (2014).
70. Oosting M, Cheng SC, Bolscher JM et al. Human TLR10 is an anti-inflammatory pattern-recognition receptor. Proc. Natl Acad. Sci. USA 111(42), E4478-E4484 (2014).
71. Lee SM, Kok KH, Jaume M et al. Toll-like receptor 10 is involved in induction of innate immune responses to influenza virus infection. Proc. Natl Acad. Sci. USA 111(10), 3793-3798 (2014).
72. Regan T, Nally K, Carmody R et al. Identification of TLR10 as a key mediator of the inflammatory response to Listeria monocytogenes in intestinal epithelial cells and macrophages. J. Immunol. 191(12), 6084-6092 (2013).
73. Wurfel MM, Gordon AC, Holden TD et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am. J. Respir. Crit. Care Med. 178(7), 710-720 (2008).
74. Ben-Ali M, Corre B, Manry J et al. Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family. Hum. Mutat. 32(6), 643-652 (2011).
75. Xiong Y, Song C, Snyder GA, Sundberg EJ, Medvedev AE. R753Q polymorphism inhibits Toll-like receptor (TLR) 2 tyrosine phosphorylation, dimerization with TLR6, and recruitment of myeloid differentiation primary response protein 88. J. Biol. Chem. 287(45), 38327-38337 (2012).
76. Mrabet-Dahbi S, Dalpke AH, Niebuhr M et al. The Toll-like receptor 2 R753Q mutation modifies cytokine production and Toll-like receptor expression in atopic dermatitis. J. Allergy Clin. Immunol. 121(4), 1013-1019 (2008).
77. Shey MS, Randhawa AK, Bowmaker M et al. Single nucleotide polymorphisms in Toll-like receptor 6 are associated with altered lipopeptide-and mycobacteria-induced interleukin-6 secretion. Genes Immun. 11(7), 561-572 (2010).
78. Mikacenic C, Reiner AP, Holden TD, Nickerson DA, Wurfel MM. Variation in the TLR10/TLR1/TLR6 locus is the major genetic determinant of interindividual difference in TLR1/2-mediated responses. Genes Immun. 14(1), 52-57 (2013).
79. Ohto U, Yamakawa N, Akashi-Takamura S, Miyake K, Shimizu T. Structural analyses of human Toll-like receptor 4 polymorphisms D299G and T399I. J. Biol. Chem. 287(48), 40611-40617 (2012).
80. Ferwerda B, Mccall MB, Alonso S et al. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc. Natl Acad. Sci. USA 104(42), 16645-16650 (2007).
81. Arbour NC, Lorenz E, Schutte BC et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet. 25(2), 187-191 (2000).
82. Figueroa L, Xiong Y, Song C, Piao W, Vogel SN, Medvedev AE. The Asp299Gly polymorphism alters TLR4 signaling by interfering with recruitment of MyD88 and TRIF. J. Immunol. 188(9), 4506-4515 (2012).
83. Long H, O'Connor BP, Zemans RL, Zhou X, Yang IV, Schwartz DA. The Toll-like receptor 4 polymorphism Asp299Gly but not Thr399Ile influences TLR4 signaling and function. PLoS ONE 9(4), e93550 (2014).
84. Erridge C, Stewart J, Poxton IR. Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the Toll-like receptor 4 gene show no deficit in lipopolysaccharide signalling. J. Exp. Med. 197(12), 1787-1791 (2003).
85. Van Der Graaf C, Kullberg BJ, Joosten L et al. Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism. Cytokine 30(5), 264-268 (2005).
86. Kumpf O, Hamann L, Schlag PM, Schumann RR. Pre-and postoperative cytokine release after in vitro whole blood lipopolysaccharide stimulation and frequent Toll-like receptor 4 polymorphisms. Shock 25(2), 123-128 (2006).
87. Schippers EF, Van 't Veer C, Van Voorden S, Martina CA, Le Cessie S, Van Dissel JT. TNF-alpha promoter, Nod2 and Toll-like receptor-4 polymorphisms and the in vivo and ex vivo response to endotoxin. Cytokine 26(1), 16-24 (2004).
88. Heesen M, Bloemeke B, Kunz D. The cytokine synthesis by heterozygous carriers of the Toll-like receptor 4 Asp299Gly polymorphism does not differ from that of wild type homozygotes. Eur. Cytokine Netw. 14(4), 234-237 (2003).
89. Calvano JE, Bowers DJ, Coyle SM et al. Response to systemic endotoxemia among humans bearing polymorphisms of the Toll-like receptor 4 (hTLR4). Clin. Immunol. 121(2), 186-190 (2006).
90. Ferwerda B, Mccall MB, Verheijen K et al. Functional consequences of Toll-like receptor 4 polymorphisms. Mol. Med. 14(5-6), 346-352 (2008).
91. Ranjith-Kumar CT, Miller W, Sun J et al. Effects of single nucleotide polymorphisms on Toll-like receptor 3 activity and expression in cultured cells. J. Biol. Chem. 282(24), 17696-17705 (2007).
92. Nahum A, Dadi H, Bates A, Roifman CM. The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity. J. Allergy Clin. Immunol. 127(2), 528-531 (2011).
93. Clifford HD, Yerkovich ST, Khoo SK et al. TLR3 and RIG-I gene variants: associations with functional effects on receptor expression and responses to measles virus and vaccine in vaccinated infants. Hum. Immunol. 73(6), 677-685 (2012).
94. Yang CA, Raftery MJ, Hamann L et al. Association of TLR3-hyporesponsiveness and functional TLR3 L412F polymorphism with recurrent herpes labialis. Hum. Immunol. 73(8), 844-851 (2012).
95. Gantier MP, Irving AT, Kaparakis-Liaskos M et al. Genetic modulation of TLR8 response following bacterial phagocytosis. Hum. Mutat. 31(9), 1069-1079 (2010).
96. Oh DY, Taube S, Hamouda O et al. A functional Toll-like receptor 8 variant is associated with HIV disease restriction. J. Infect. Dis. 198(5), 701-709 (2008).
97. Ng MT, Van't Hof R, Crockett JC et al. Increase in NF-kappaB binding affinity of the variant C allele of the Toll-like receptor 9-1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease. Infect. Immun. 78(3), 1345-1352 (2010).
98. Carvalho A, Osorio NS, Saraiva M et al. The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation. PLoS ONE 6(11), e28256 (2011).
99. Picard C, Von Bernuth H, Ghandil P et al. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine 89(6), 403-425 (2010).
100. Picard C, Casanova JL, Puel A. Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IkappaBalpha deficiency. Clin. Microbiol. Rev. 24(3), 490-497 (2011).
101. Picard C, Puel A, Bonnet M et al. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299(5615), 2076-2079 (2003).
102. Von Bernuth H, Picard C, Jin Z et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321(5889), 691-696 (2008).
103. Bousfiha A, Picard C, Boisson-Dupuis S et al. Primary immunodeficiencies of protective immunity to primary infections. Clin. Immunol. 135(2), 204-209 (2010).
104. Zhang SY, Jouanguy E, Ugolini S et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science 317(5844), 1522-1527 (2007).
105. Perez De Diego R, Sancho-Shimizu V, Lorenzo L et al. Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity 33(3), 400-411 (2010).
106. Sancho-Shimizu V, Perez De Diego R, Lorenzo L et al. Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J. Clin. Invest. 121(12), 4889-4902 (2011).
107. Casrouge A, Zhang SY, Eidenschenk C et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314(5797), 308-312 (2006).
108. Brown GD, Herre J, Williams DL, Willment JA, Marshall AS, Gordon S. Dectin-1 mediates the biological effects of betaglucans. J. Exp. Med. 197(9), 1119-1124 (2003).
109. Kerscher B, Willment JA, Brown GD. The Dectin-2 family of C-type lectin-like receptors: an update. Int. Immunol. 25(5), 271-277 (2013).
110. Gringhuis SI, Wevers BA, Kaptein TM et al. Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2. PLoS Pathog. 7(1), e1001259 (2011).
111. Sancho D, Reis E, Sousa C. Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Ann. Rev. Immmunol. 30, 491-529 (2012).
112. Kankkunen P, Teirila L, Rintahaka J, Alenius H, Wolff H, Matikainen S. (1,3)-beta-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. J. Immunol. 184(11), 6335-6342 (2010).
113. Plantinga TS, Van Der Velden WJ, Ferwerda B et al. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin. Infect. Dis. 49(5), 724-732 (2009).
114. Ferwerda B, Ferwerda G, Plantinga TS et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N. Engl. J. Med. 361(18), 1760-1767 (2009).
115. Plantinga TS, Hamza OJ, Willment JA et al. Genetic variation of innate immune genes in HIV-infected African patients with or without oropharyngeal candidiasis. J. Acquir. Immune Defic. Syndr. 55(1), 87-94 (2010).
116. Cunha C, Di Ianni M, Bozza S et al. Dectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient-and donordependent mechanisms of antifungal immunity. Blood 116(24), 5394-5402 (2010).
117. Chai LY, De Boer MG, Van Der Velden WJ et al. The Y238X stop codon polymorphism in the human beta-glucan receptor dectin-1 and susceptibility to invasive aspergillosis. J. Infect. Dis. 203(5), 736-743 (2011).
118. Sainz J, Lupianez CB, Segura-Catena J et al. Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary aspergillosis infection. PLoS ONE 7(2), e32273 (2012).
119. Barreiro LB, Neyrolles O, Babb CL et al. Promoter variation in the DC-SIGNencoding gene CD209 is associated with tuberculosis. PLoS Med. 3(2), e20 (2006).
120. Martin MP, Lederman MM, Hutcheson HB et al. Association of DC-SIGN promoter polymorphism with increased risk for parenteral, but not mucosal, acquisition of human immunodeficiency virus type 1 infection. J. Virol. 78(24), 14053-14056 (2004).
121. Sakuntabhai A, Turbpaiboon C, Casademont I et al. A variant in the CD209 promoter is associated with severity of Dengue disease. Nat. Genet. 37(5), 507-513 (2005).
122. Zhang X, Jiang F, Wei L et al. Polymorphic allele of human MRC1 confer protection against tuberculosis in a Chinese population. Int. J. Biol. Sci. 8(3), 375-382 (2012).
123. Alter A, De Leseleuc L, Nguyen VT et al. Genetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy susceptibility. Hum. Genet. 127(3), 337-348 (2010).
124. Wang D, Feng JQ, Li YY et al. Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy in Han Chinese from Southwest China. Hum. Genet. 131(7), 1251-1260 (2012).
125. Cunha C, Aversa F, Lacerda JF et al. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 370(5), 421-432 (2014).
126. Olesen R, Wejse C, Velez DR et al. DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun. 8(6), 456-467 (2007).
127. Chiarini M, Sabelli C, Melotti P et al. PTX3 genetic variations affect the risk of Pseudomonas aeruginosa airway colonization in cystic fibrosis patients. Genes Immun. 11(8), 665-670 (2010).
128. Giraldo PC, Babula O, Goncalves AKS et al. Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis. Obstet. Gynecol. 109(5), 1123-1128 (2007).
129. Donders GGG, Babula O, Bellen G, Linhares IM, Witkin SS. Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis. BJOG 115(10), 1225-1231 (2008).
130. Wojitani MDKH, De Aguiar LM, Baracat EC, Linhares IM. Association between mannose-binding lectin and interleukin-1 receptor antagonist gene polymorphisms and recurrent vulvovaginal candidiasis. Arch. Gynecol. Obstet. 285(1), 149-153 (2012).
131. Babula O, Lazdane G, Kroica J, Ledger WJ, Witkin SS. Relation between recurrent vulvovaginal candidiasis, vaginal concentrations of mannose-binding lectin, and a mannose-binding lectin gene polymorphism in latvian women. Clin. Infect. Dis. 37(5), 733-737 (2003).
132. Glocker EO, Hennigs A, Nabavi M et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 361(18), 1727-1735 (2009).
133. Lanternier F, Pathan S, Vincent QB et al. Deep dermatophytosis and inherited CARD9 deficiency. N. Engl. J. Med. 369(18), 1704-1714 (2013).
134. Gavino C, Cotter A, Lichtenstein D et al. CARD9 deficiency and spontaneous central nervous system candidiasis: complete clinical remission with GM-CSF therapy. Clin. Infect. Dis. 59(1), 81-84 (2014).
135. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J. Exp. Med. 197(9), 1107-1117 (2003).
136. Dennehy KM, Ferwerda G, Faro-Trindade I et al. Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors. Eur. J. Immunol. 38(2), 500-506 (2008).
137. Ferwerda G, Meyer-Wentrup F, Kullberg BJ, Netea MG, Adema GJ. Dectin-1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages. Cell. Microbiol. 10(10), 2058-2066 (2008).
138. Taylor PR, Tsoni SV, Willment JA et al. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat. Immunol. 8(1), 31-38 (2007).
139. Usluogullari B, Gumus I, Gunduz E et al. The role of human Dectin-1 Y238X gene polymorphism in recurrent vulvovaginal candidiasis infections. Mol. Biol. Rep. 41(10), 6763-6768 (2014).
140. Den Dunnen J, Gringhuis SI, Geijtenbeek TB. Innate signaling by the C-type lectin DC-SIGN dictates immune responses. Cancer Immunol. Immunother. 58(7), 1149-1157 (2009).
141. Koizumi Y, Kageyama S, Fujiyama Y et al. RANTES-28G delays and DC-SIGN-139C enhances AIDS progression in HIV type 1-infected Japanese hemophiliacs. AIDS Res. Hum. Retroviruses 23(5), 713-719 (2007).
142. Azad AK, Sadee W, Schlesinger LS. Innate immune gene polymorphisms in tuberculosis. Infect. Immun. 80(10), 3343-3359 (2012).
143. Miao R, Li J, Sun Z, Li C, Xu F. Association between the CD209 promoter-336A/G polymorphism and susceptibility to tuberculosis: a meta-analysis. Respirology 17(5), 847-853 (2012).
144. Garlanda C, Bottazzi B, Bastone A, Mantovani A. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Ann. Rev. Immmunol. 23, 337-366 (2005).
145. Garlanda C, Hirsch E, Bozza S et al. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420(6912), 182-186 (2002).
146. Moalli F, Doni A, Deban L et al. Role of complement and Fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus. Blood 116(24), 5170-5180 (2010).
147. Tierney L, Linde J, Muller S et al. An interspecies regulatory network inferred from simultaneous RNA-seq of Candida albicans invading innate immune cells. Front. Microbiol. 3, 85 (2012).
148. Diniz SN, Nomizo R, Cisalpino PS et al. PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages. J. Leukoc. Biol. 75(4), 649-656 (2004).
149. De Boer MG, Halkes CJ, Van De Vosse E. PTX3 deficiency and aspergillosis. N. Engl. J. Med. 370(17), 1665-1666 (2014).
150. Stahl PD, Ezekowitz RaB. The mannose receptor is a pattern recognition receptor involved in host defense. Curr. Opin. Immunol. 10(1), 50-55 (1998).
151. Fraser IP, Koziel H, Ezekowitz RaB. The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity. Semin. Immunol. 10(5), 363-372 (1998).
152. Turner MW. Mannose-binding lectin: the pluripotent molecule of the innate immune system (vol 17, pg 532, 1996). Immunol. Today 18(2), 98-98 (1997).
153. Lipscombe RJ, Sumiya M, Summerfield JA, Turner MW. Distinct physicochemical characteristics of human mannose-binding protein expressed by individuals of differing genotype. Immunology 85(4), 660-667 (1995).
154. Liu F, Liao QP, Liu ZH. Mannose-binding lectin and vulvovaginal candidiasis. Int. J. Gynecol. Obstet. 92(1), 43-47 (2006).
155. Babula O, Lazdane G, Kroica J, Linhares IM, Ledger WJ, Witkin SS. Frequency of interleukin-4 (IL-4)-589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis. Clin. Infect. Dis. 40(9), 1258-1262 (2005).
156. Lambourne J, Agranoff D, Herbrecht R et al. Association of mannose-binding lectin deficiency with acute invasive aspergillosis in immunocompromised patients. Clin. Infect. Dis. 49(10), 1486-1491 (2009).
157. Crosdale DJ, Poulton KV, Ollier WE, Thomson W, Denning DW. Mannosebinding lectin gene polymorphisms as a susceptibility factor for chronic necrotizing pulmonary aspergillosis. J. Infect. Dis. 184(5), 653-656 (2001).
158. Sabbah A, Chang TH, Harnack R et al. Activation of innate immune antiviral responses by Nod2. Nat. Immunol. 10(10), 1073-1080 (2009).
159. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Ann. Rev. Immmunol. 27, 229-265 (2009).
160. Proell M, Riedl SJ, Fritz JH, Rojas AM, Schwarzenbacher R. The Nod-like receptor (NLR) family: a tale of similarities and differences. PLoS ONE 3(4), e2119 (2008).
161. Tschopp J, Martinon F, Burns K. NALPs: a novel protein family involved in inflammation. Nat. Rev. Mol. Cell Biol. 4(2), 95-104 (2003).
162. Inohara N, Ogura Y, Fontalba A et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J. Biol. Chem. 278(8), 5509-5512 (2003).
163. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher MA. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J. Biol. Chem. 282(50), 36223-36229 (2007).
164. Hugot JP, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411(6837), 599-603 (2001).
165. Ogura Y, Bonen DK, Inohara N et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411(6837), 603-606 (2001).
166. Tekin D, Dalgic N, Kayaalti Z, Soylemezoglu T, Diler B, Kutlubay BI. Importance of NOD2/CARD15 gene variants for susceptibility to and outcome of sepsis in Turkish children. Pediatr. Crit. Care Med. 13(2), e73-e77 (2012).
167. Austin CM, Ma X, Graviss EA. Common nonsynonymous polymorphisms in the NOD2 gene are associated with resistance or susceptibility to tuberculosis disease in African Americans. J. Infect. Dis. 197(12), 1713-1716 (2008).
168. Zhang FR, Huang W, Chen SM et al. Genomewide association study of leprosy. N. Engl. J. Med. 361(27), 2609-2618 (2009).
169. Grant AV, Alter A, Huong NT et al. Crohn's disease susceptibility genes are associated with leprosy in the Vietnamese population. J. Infect. Dis. 206(11), 1763-1767 (2012).
170. Berrington WR, Macdonald M, Khadge S et al. Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states. J. Infect. Dis. 201(9), 1422-1435 (2010).
171. Sung HJ, Chung WC, Kim EJ et al. Association between genetic polymorphisms of NOD1 and Helicobacter pylori-induced gastric mucosal inflammation. J. Gastroenterol. Hepatol. 27, 404-404 (2012).
172. Witkin SS, Bierhals K, Linhares I, Normand N, Dieterle S, Neuer A. Genetic polymorphism in an inflammasome component, cervical mycoplasma detection and female infertility in women undergoing in vitro fertilization. J. Reprod. Immunol. 84(2), 171-175 (2010).
173. Lev-Sagie A, Prus D, Linhares IM, Lavy Y, Ledger WJ, Witkin SS. Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome. Am. J. Obstetr. Gynecol. 200(3), 303.e1-e6 (2009).
174. Wang W, Stassen FR, Surcel HM et al. Analyses of polymorphisms in the inflammasome-associated NLRP3 and miRNA-146A genes in the susceptibility to and tubal pathology of Chlamydia trachomatis infection. Drugs Today 45(Suppl. B), 95-103 (2009).
175. Travassos LH, Carneiro LA, Ramjeet M et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11(1), 55-62 (2010).
176. Cooney R, Baker J, Brain O et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16(1), 90-97 (2010).
177. Molnar T, Hofner P, Nagy F et al. NOD1 gene E266K polymorphism is associated with disease susceptibility but not with disease phenotype or NOD2/CARD15 in Hungarian patients with Crohn's disease. Dig. Liver Dis. 39(12), 1064-1070 (2007).
178. Mcgovern DP, Hysi P, Ahmad T et al. Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum. Mol. Genet. 14(10), 1245-1250 (2005).
179. Franke A, Ruether A, Wedemeyer N, Karlsen TH, Nebel A, Schreiber S. No association between the functional CARD4 insertion/deletion polymorphism and inflammatory bowel diseases in the German population. Gut 55(11), 1679-1680 (2006).
180. Van Limbergen J, Russell RK, Nimmo ER et al. Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe. Inflamm. Bowel Dis. 13(7), 882-889 (2007).
181. Van Limbergen J, Nimmo ER, Russell RK et al. Investigation of NOD1/CARD4 variation in inflammatory bowel disease using a haplotype-tagging strategy. Hum. Mol. Genet. 16(18), 2175-2186 (2007).
182. Hysi P, Kabesch M, Moffatt MF et al. NOD1 variation, immunoglobulin E and asthma. Hum. Mol. Genet. 14(7), 935-941 (2005).
183. Agostini L, Martinon F, Burns K, Mcdermott MF, Hawkins PN, Tschopp J. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20(3), 319-325 (2004).
184. Yang CS, Shin DM, Jo EK. The role of NLR-related protein 3 inflammasome in host defense and inflammatory diseases. Int. Neurol. J. 16(1), 2-12 (2012).
185. Go S, Yoneyama M, Fujita T. [Structural and functional views of the intracellular viral RNA sensor RIG-I]. Uirusu 58(2), 97-103 (2008).
186. Yoneyama M, Kikuchi M, Matsumoto K et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J. Immunol. 175(5), 2851-2858 (2005).
187. Kovacsovics M, Martinon F, Micheau O, Bodmer JL, Hofmann K, Tschopp J. Overexpression of Helicard, a CARDcontaining helicase cleaved during apoptosis, accelerates DNA degradation. Curr. Biol. 12(10), 838-843 (2002).
188. Lamkanfi M, Vande Walle L, Kanneganti TD. Deregulated inflammasome signaling in disease. Immunol. Rev. 243(1), 163-173 (2011).
189. Saito T, Hirai R, Loo YM et al. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc. Natl Acad. Sci. USA 104(2), 582-587 (2007).
190. Hu J, Nistal-Villan E, Voho A et al. A common polymorphism in the caspase recruitment domain of RIG-I modifies the innate immune response of human dendritic cells. J. Immunol. 185(1), 424-432 (2010).
191. Ovsyannikova IG, Haralambieva IH, Dhiman N et al. Polymorphisms in the vitamin A receptor and Innate Immun. genes influence the antibody response to rubella vaccination. J. Infect. Dis. 201(2), 207-213 (2010).
192. Pothlichet J, Burtey A, Kubarenko AV et al. Study of human RIG-I polymorphisms identifies two variants with an opposite impact on the antiviral immune response. PLoS ONE 4(10), e7582 (2009).
193. Jaeger M, Van Der Lee R, Cheng SC et al. The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections. Eur. J. Clin. Microbiol. Infect. Dis. (2015) (Epub ahead of print).
194. Robinson T, Kariuki SN, Franek BS et al. Autoimmune disease risk variant of IFIH1 is associated with increased sensitivity to IFN-alpha and serologic autoimmunity in lupus patients. J. Immunol. 187(3), 1298-1303 (2011).
195. Ferreira RC, Pan-Hammarstrom Q, Graham RR et al. Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. Nat. Genet. 42(9), 777-780 (2010).
196. Molineros JE, Maiti AK, Sun C et al. Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production. PLoS Genet. 9(2), e1003222 (2013).
197. Downes K, Pekalski M, Angus KL et al. Reduced expression of IFIH1 is protective for type 1 diabetes. PLoS ONE 5(9), pii: e12646 (2010).
198. Liu S, Wang H, Jin Y et al. IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells. Hum. Mol. Genet. 18(2), 358-365 (2009).
199. Muruve DA, Petrilli V, Zaiss AK et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452(7183), 103-107 (2008).
200. Hornung V, Ablasser A, Charrel-Dennis M et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458(7237), 514-518 (2009).
201. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458(7237), 509-513 (2009).