Leishmania and the macrophage: A multifaceted interaction

Future Microbiology

Volumn 10, Issue 1, 2015, Pages 111-129

  Podinovskaia, Maria ^a   Descoteaux, Albert ^a  

^a Department of Microbiology and Immunology   (Canada)

Author keywords

GP63; Leishmania; lipophosphoglycan; macrophage; phagocytosis; phagosome

Indexed keywords

GP63 PROTEIN; LIPOPHOSPHOGLYCAN; METALLOPROTEINASE; SERINE PROTEINASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIGEN PRESENTATION; ANTIGEN RECOGNITION; AUTOPHAGY; CELL DAMAGE; CELL DIFFERENTIATION; CELL MATURATION; CELL SURVIVAL; ENDOPLASMIC RETICULUM; HOST PARASITE INTERACTION; HOST RESISTANCE; HUMAN; INTRACELLULAR SIGNALING; LEISHMANIA; MACROPHAGE; MACROPHAGE ACTIVATION; MICROBIAL GROWTH; NONHUMAN; OXIDATIVE STRESS; PHAGOSOME; PRIORITY JOURNAL; REVIEW; SURVIVAL FACTOR; APOPTOSIS; IMMUNE EVASION; IMMUNOLOGY; LEISHMANIASIS; PARASITOLOGY; PATHOGENICITY; PHYSIOLOGY;

PHLEBOTOMINAE; PROTOZOA;

ANTIGEN PRESENTATION; APOPTOSIS; HOST-PARASITE INTERACTIONS; HUMANS; IMMUNE EVASION; LEISHMANIA; LEISHMANIASIS; MACROPHAGE ACTIVATION; MACROPHAGES; PHAGOSOMES;

EID: 84921531621     PISSN: 17460913     EISSN: 17460921     Source Type: Journal    
DOI: 10.2217/fmb.14.103     Document Type: Review

References (107)

1. De Oliveira CI, Brodskyn CI. The immunobiology of Leishmania braziliensis infection. Front. Immunol. 3, 145 (2012).
2. Bates PA. Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies. Int. J. Parasitol. 37(10), 1097-1106 (2007).
3. Peters NC, Egen JG, Secundino N et al. In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies. Science 321(5891), 970-974 (2008).
4. Rogers M, Kropf P, Choi BS et al. Proteophosophoglycans regurgitated by Leishmania-infected sand flies target the L-arginine metabolism of host macrophages to promote parasite survival. PLoS Pathog. 5(8), e1000555 (2009).
5. Rogers ME, Corware K, Muller I, Bates PA. Leishmania infantum proteophosphoglycans regurgitated by the bite of its natural sand fly vector, Lutzomyia longipalpis, promote parasite establishment in mouse skin and skin-distant tissues. Microbes Infect. 12(11), 875-879 (2010).
6. Peters NC, Sacks DL. The impact of vector-mediated neutrophil recruitment on cutaneous leishmaniasis. Cell. Microbiol. 11(9), 1290-1296 (2009).
7. Mollinedo F, Janssen H, De La Iglesia-Vicente J, Villa-Pulgarin JA, Calafat J. Selective fusion of azurophilic granules with Leishmania-containing phagosomes in human neutrophils. J. Biol. Chem. 285(45), 34528-34536 (2010).
8. Beattie L, Kaye PM. Leishmania-host interactions: what has imaging taught us? Cell. Microbiol. 13(11), 1659-1667 (2011).
9. Rotureau B, Morales MA, Bastin P, Spath GF. The flagellum-mitogen-activated protein kinase connection in trypanosomatids: a key sensory role in parasite signalling and development? Cell. Microbiol. 11(5), 710-718 (2009).
10. Forestier CL, Machu C, Loussert C, Pescher P, Spath GF. Imaging host cell-Leishmania interaction dynamics implicates parasite motility, lysosome recruitment, and host cell wounding in the infection process. Cell Host Microbe 9(4), 319-330 (2011).
11. Ueno N, Wilson ME. Receptor-mediated phagocytosis of Leishmania: implications for intracellular survival. Trends Parasitol. 28(8), 335-344 (2012).
12. Polando R, Dixit UG, Carter CR et al. The roles of complement receptor 3 and Fcgamma receptors during Leishmania phagosome maturation. J. Leukoc. Biol. 93(6), 921-932 (2013).
13. Rodriguez NE, Gaur Dixit U, Allen LA, Wilson ME. Stage-specific pathways of Leishmania infantum chagasi entry and phagosome maturation in macrophages. PLoS ONE 6(4), e19000 (2011).
14. Chattopadhyay A, Jafurulla M. Role of membrane cholesterol in leishmanial infection. Adv. Exp. Med. Biol. 749, 201-213 (2012).
15. Roy S, Kumar GA, Jafurulla M, Mandal C, Chattopadhyay A. Integrity of the Actin Cytoskeleton of Host Macrophages is Essential for Leishmania donovani Infection. Biochim. Biophys. Acta 1838(8), 2011-2018 (2014).
16. Pucadyil TJ, Tewary P, Madhubala R, Chattopadhyay A. Cholesterol is required for Leishmania donovani infection: implications in leishmaniasis. Mol. Biochem. Parasitol. 133(2), 145-152 (2004).
17. Pucadyil TJ, Chattopadhyay A. Cholesterol: a potential therapeutic target in Leishmania infection? Trends Parasitol. 23(2), 49-53 (2007).
18. Majumder S, Dey R, Bhattacharjee S et al. Leishmania-induced biphasic ceramide generation in macrophages is crucial for uptake and survival of the parasite. J. Infect. Dis. 205(10), 1607-1616 (2012).
19. Moradin N, Descoteaux A. Leishmania promastigotes: building a safe niche within macrophages. Front. Cell Infect. Microbiol. 2, 121 (2012).
20. Vinet AF, Fukuda M, Turco SJ, Descoteaux A. The Leishmania donovani lipophosphoglycan excludes the vesicular proton-ATPase from phagosomes by impairing the recruitment of synaptotagmin V. PLoS Pathog. 5(10), e1000628 (2009).
21. Mittra B, Andrews NW. IRONy OF FATE: role of iron-mediated ROS in Leishmania differentiation. Trends Parasitol. 29(10), 489-496 (2013).
22. Mittra B, Cortez M, Haydock A, Ramasamy G, Myler PJ, Andrews NW. Iron uptake controls the generation of Leishmania infective forms through regulation of ROS levels. J. Exp. Med. 210(2), 401-416 (2013).
23. Flannery AR, Huynh C, Mittra B, Mortara RA, Andrews NW. LFR1 ferric iron reductase of Leishmania amazonensis is essential for the generation of infective parasite forms. J. Biol. Chem. 286(26), 23266-23279 (2011).
24. Saunders EC, Ng WW, Kloehn J, Chambers JM, Ng M, Mcconville MJ. Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism. PLoS Pathog. 10(1), e1003888 (2014).
25. Real F, Mortara RA, Rabinovitch M. Fusion between Leishmania amazonensis and Leishmania major parasitophorous vacuoles: live imaging of coinfected macrophages. PLoS Negl. Trop. Dis. 4(12), e905 (2010).
26. Boggiatto PM, Jie F, Ghosh M et al. Altered dendritic cell phenotype in response to Leishmania amazonensis amastigote infection is mediated by MAP kinase, ERK. Am. J. Pathol 174(5), 1818-1826 (2009).
27. Real F, Mortara RA. The diverse and dynamic nature of Leishmania parasitophorous vacuoles studied by multidimensional imaging. PLoS Negl. Trop. Dis. 6(2), e1518 (2012).
28. Canton J, Kima PE. Interactions of pathogen-containing compartments with the secretory pathway. Cell. Microbiol. 14(11), 1676-1686 (2012).
29. Ndjamen B, Kang BH, Hatsuzawa K, Kima PE. Leishmania parasitophorous vacuoles interact continuously with the host cell's endoplasmic reticulum; parasitophorous vacuoles are hybrid compartments. Cell. Microbiol. 12(10), 1480-1494 (2010).
30. Canton J, Ndjamen B, Hatsuzawa K, Kima PE. Disruption of the fusion of Leishmania parasitophorous vacuoles with ER vesicles results in the control of the infection. Cell. Microbiol. 14(6), 937-948 (2012).
31. Canton J, Kima PE. Targeting host syntaxin-5 preferentially blocks Leishmania parasitophorous vacuole development in infected cells and limits experimental Leishmania infections. Am. J. Pathol. 181(4), 1348-1355 (2012).
32. Stechmann B, Bai SK, Gobbo E et al. Inhibition of retrograde transport protects mice from lethal ricin challenge. Cell 141(2), 231-242 (2010).
33. Cebrian I, Visentin G, Blanchard N et al. Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells. Cell 147(6), 1355-1368 (2011).
34. Besteiro S, Williams RA, Coombs GH, Mottram JC. Protein turnover and differentiation in Leishmania. Int. J. Parasitol. 37(10), 1063-1075 (2007).
35. Naderer T, Mcconville MJ. The Leishmania-macrophage interaction: a metabolic perspective. Cell. Microbiol. 10(2), 301-308 (2008).
36. Pinheiro RO, Nunes MP, Pinheiro CS et al. Induction of autophagy correlates with increased parasite load of Leishmania amazonensis in BALB/c but not C57BL/6 macrophages. Microbes Infect 11(2), 181-190 (2009).
37. Rabhi I, Rabhi S, Ben-Othman R et al. Transcriptomic signature of Leishmania infected mice macrophages: a metabolic point of view. PLoS Negl. Trop. Dis. 6(8), e1763 (2012).
38. Lecoeur H, Giraud E, Prevost MC, Milon G, Lang T. Reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live Leishmania amazonensis amastigotes. PLoS Negl. Trop. Dis. 7(6), e2276 (2013).
39. Araujo-Santos T, Prates DB, Andrade BB et al. Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E(2) production in murine macrophages. PLoS Negl. Trop. Dis. 4(11), e873 (2010).
40. Podinovskaia M, Lee W, Caldwell S, Russell DG. Infection of macrophages with Mycobacterium tuberculosis induces global modifications to phagosomal function. Cell. Microbiol. 15(6), 843-859 (2013).
41. Melo RC, Dvorak AM. Lipid body-phagosome interaction in macrophages during infectious diseases: host defense or pathogen survival strategy? PLoS Pathog. 8(7), e1002729 (2012).
42. Flannery AR, Renberg RL, Andrews NW. Pathways of iron acquisition and utilization in Leishmania. Curr. Opin. Microbiol. 16(6), 716-721 (2013).
43. Miguel DC, Flannery AR, Mittra B, Andrews NW. Heme uptake mediated by LHR1 is essential for Leishmania amazonensis virulence. Infect. Immun. 81(10), 3620-3626 (2013).
44. Marquis JF, Gros P. Intracellular Leishmania: Your iron or mine? Trends Microbiol. 15(3), 93-95 (2007).
45. Huynh C, Sacks DL, Andrews NW. A Leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes. J. Exp. Med. 203(10), 2363-2375 (2006).
46. Ben-Othman R, Flannery AR, Miguel DC, Ward DM, Kaplan J, Andrews NW. Leishmania-mediated inhibition of iron export promotes parasite replication in macrophages. PLoS Pathog. 10(1), e1003901 (2014).
47. Das NK, Biswas S, Solanki S, Mukhopadhyay CK. Leishmania donovani depletes labile iron pool to exploit iron uptake capacity of macrophage for its intracellular growth. Cell. Microbiol. 11(1), 83-94 (2009).
48. Lima-Junior DS, Costa DL, Carregaro V et al. Inflammasome-derived IL-1beta production induces nitric oxide-mediated resistance to Leishmania. Nat. Med. 19(7), 909-915 (2013).
49. Chaves MM, Marques-Da-Silva C, Monteiro AP, Canetti C, Coutinho-Silva R. Leukotriene B4 modulates P2X7 receptor-mediated Leishmania amazonensis elimination in murine macrophages. J. Immunol. 192(10), 4765-4773 (2014).
50. Liu D, Uzonna JE. The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response. Front. Cell. Infect. Microbiol. 2, 83 (2012).
51. Filardy AA, Costa-Da-Silva AC, Koeller CM et al. Infection with Leishmania major induces a cellular stress response in macrophages. PLoS ONE 9(1), e85715 (2014).
52. Hardy PO, Diallo TO, Matte C, Descoteaux A. Roles of phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase in the regulation of protein kinase C-alpha activation in interferon-gamma-stimulated macrophages. Immunology 128(Suppl. 1), e652-e660 (2009).
53. Gomez MA, Li S, Tremblay ML, Olivier M. NRAMP-1 expression modulates protein-tyrosine phosphatase activity in macrophages: impact on host cell signaling and functions. J. Biol. Chem. 282(50), 36190-36198 (2007).
54. Gomez CP, Tiemi Shio M, Duplay P, Olivier M, Descoteaux A. The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis. J. Immunol. 189(5), 2203-2210 (2012).
55. Yates RM, Hermetter A, Taylor GA, Russell DG. Macrophage activation downregulates the degradative capacity of the phagosome. Traffic 8(3), 241-250 (2007).
56. Reis LC, Ramos-Sanchez EM, Goto H. The interactions and essential effects of intrinsic insulin-like growth factor-I on Leishmania (Leishmania) major growth within macrophages. Parasite Immunol. 35(7-8), 239-244 (2013).
57. Bougneres L, Helft J, Tiwari S et al. A role for lipid bodies in the cross-presentation of phagocytosed antigens by MHC class I in dendritic cells. Immunity 31(2), 232-244 (2009).
58. Lapara NJ, 3rd, Kelly BL. Suppression of LPS-induced inflammatory responses in macrophages infected with Leishmania. J. Inflamm. 7(1), 8 (2013).
59. Gomez MA, Olivier M. Proteases and phosphatases during Leishmania-macrophage interaction: paving the road for pathogenesis. Virulence 1(4), 314-318 (2010).
60. Ibraim IC, De Assis RR, Pessoa NL et al. Two biochemically distinct lipophosphoglycans from Leishmania braziliensis and Leishmania infantum trigger different innate immune responses in murine macrophages. Parasit. Vectors 6, 54 (2013).
61. Isnard A, Shio MT, Olivier M. Impact of Leishmania metalloprotease GP63 on macrophage signaling. Front. Cell. Infect. Microbiol. 2, 72 (2012).
62. Gupta P, Giri J, Srivastav S et al. Leishmania donovani targets tumor necrosis factor receptor-associated factor (TRAF) 3 for impairing TLR4-mediated host response. FASEB J. 28(4), 1756-1768 (2014).
63. Eschenlauer SC, Faria MS, Morrison LS et al. Influence of parasite encoded inhibitors of serine peptidases in early infection of macrophages with Leishmania major. Cell. Microbiol. 11(1), 106-120 (2009).
64. Faria MS, Calegari-Silva TC, De Carvalho Vivarini A, Mottram JC, Lopes UG, Lima AP. Role of protein kinase R in the killing of Leishmania major by macrophages in response to neutrophil elastase and TLR4 via TNFalpha and IFNbeta. FASEB J. 28(7), 3050-3063 (2014).
65. Chan MM, Adapala N, Chen C. Peroxisome Proliferator-Activated Receptor-gamma-Mediated Polarization of Macrophages in Leishmania Infection. PPAR Res. 2012, 796235 (2012).
66. Ball WB, Mukherjee M, Srivastav S, Das PK. Leishmania donovani activates uncoupling protein 2 transcription to suppress mitochondrial oxidative burst through differential modulation of SREBP2, Sp1 and USF1 transcription factors. Int. J. Biochem. Cell Biol. 48, 66-76 (2014).
67. Matheoud D, Moradin N, Bellemare-Pelletier A et al. Leishmania evades host immunity by inhibiting antigen cross-presentation through direct cleavage of the SNARE VAMP8. Cell Host Microbe 14(1), 15-25 (2013).
68. Lodge R, Diallo TO, Descoteaux A. Leishmania donovani lipophosphoglycan blocks NADPH oxidase assembly at the phagosome membrane. Cell. Microbiol. 8(12), 1922-1931 (2006).
69. Cyrino LT, Araujo AP, Joazeiro PP, Vicente CP, Giorgio S. In vivo and in vitro Leishmania amazonensis infection induces autophagy in macrophages. Tissue Cell 44(6), 401-408 (2012).
70. Meier CL, Svensson M, Kaye PM. Leishmania-induced inhibition of macrophage antigen presentation analyzed at the single-cell level. J. Immunol. 171(12), 6706-6713 (2003).
71. Chakraborty D, Banerjee S, Sen A, Banerjee KK, Das P, Roy S. Leishmania donovani affects antigen presentation of macrophage by disrupting lipid rafts. J. Immunol. 175(5), 3214-3224 (2005).
72. Rybicka JM, Balce DR, Chaudhuri S, Allan ER, Yates RM. Phagosomal proteolysis in dendritic cells is modulated by NADPH oxidase in a pH-independent manner. EMBO J. 31(4), 932-944 (2012).
73. Savina A, Jancic C, Hugues S et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell 126(1), 205-218 (2006).
74. Real F, Florentino PT, Reis LC et al. Cell-to-cell transfer of Leishmania amazonensis amastigotes is mediated by immunomodulatory LAMP-rich parasitophorous extrusions. Cell. Microbiol. 16(10), 1549-1564 (2014).
75. Shio MT, Hassani K, Isnard A et al. Host cell signalling and leishmania mechanisms of evasion. J. Trop. Med. 2012, 819512 (2012).
76. Bhattacharya P, Gupta G, Majumder S et al. Arabinosylated lipoarabinomannan skews Th2 phenotype towards Th1 during Leishmania infection by chromatin modification: Involvement of MAPK signaling. PLoS ONE 6(9), e24141 (2011).
77. Matte C, Descoteaux A. Leishmania donovani amastigotes impair gamma interferon-induced STAT1alpha nuclear translocation by blocking the interaction between STAT1alpha and importin-alpha5. Infect. Immun. 78(9), 3736-3743 (2010).
78. Olivier M, Atayde VD, Isnard A, Hassani K, Shio MT. Leishmania virulence factors: focus on the metalloprotease GP63. Microbes Infect. 14(15), 1377-1389 (2012).
79. Almeida TF, Palma LC, Mendez LC, Noronha-Dutra AA, Veras PS. Leishmania amazonensis fails to induce the release of reactive oxygen intermediates by CBA macrophages. Parasite Immunol. 34(10), 492-498 (2012).
80. Pham NK, Mouriz J, Kima PE. Leishmania pifanoi amastigotes avoid macrophage production of superoxide by inducing heme degradation. Infect. Immun. 73(12), 8322-8333 (2005).
81. Srivastav S, Basu Ball W, Gupta P, Giri J, Ukil A, Das PK. Leishmania donovani prevents oxidative burst-mediated apoptosis of host macrophages through selective induction of suppressors of cytokine signaling (SOCS) proteins. J. Biol. Chem. 289(2), 1092-1105 (2014).
82. Ghosh J, Guha R, Das S, Roy S. Liposomal cholesterol delivery activates the macrophage innate immune arm to facilitate intracellular Leishmania donovani killing. Infect. Immun. 82(2), 607-617 (2013).
83. Vinet AF, Jananji S, Turco SJ, Fukuda M, Descoteaux A. Exclusion of synaptotagmin V at the phagocytic cup by Leishmania donovani lipophosphoglycan results in decreased promastigote internalization. Microbiology 157(Pt 9), 2619-2628 (2011).
84. Winberg ME, Holm A, Sarndahl E et al. Leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts. Microbes Infect. 11(2), 215-222 (2009).
85. Rojas-Bernabe A, Garcia-Hernandez O, Maldonado-Bernal C et al. Leishmania mexicana lipophosphoglycan activates ERK and p38 MAP kinase and induces production of proinflammatory cytokines in human macrophages through TLR2 and TLR4. Parasitology 141(6), 788-800 (2014).
86. Weinkopff T, Mariotto A, Simon G et al. Role of toll-like receptor 9 signaling in experimental Leishmania braziliensis infection. Infect. Immun. 81(5), 1575-1584 (2013).
87. Srivastava S, Pandey SP, Jha MK, Chandel HS, Saha B. Leishmania expressed lipophosphoglycan interacts with Toll-like receptor (TLR)-2 to decrease TLR-9 expression and reduce anti-leishmanial responses. Clin. Exp. Immunol. 172(3), 403-409 (2013).
88. Luz NF, Andrade BB, Feijo DF et al. Heme oxygenase-1 promotes the persistence of Leishmania chagasi infection. J. Immunol. 188(9), 4460-4467 (2012).
89. Contreras I, Gomez MA, Nguyen O, Shio MT, Mcmaster RW, Olivier M. Leishmania-induced inactivation of the macrophage transcription factor AP-1 is mediated by the parasite metalloprotease GP63. PLoS Pathog. 6(10), e1001148 (2010).
90. Halle M, Gomez MA, Stuible M et al. The Leishmania surface protease GP63 cleaves multiple intracellular proteins and actively participates in p38 mitogen-activated protein kinase inactivation. J. Biol. Chem. 284(11), 6893-6908 (2009).
91. Jaramillo M, Gomez MA, Larsson O et al. Leishmania repression of host translation through mTOR cleavage is required for parasite survival and infection. Cell Host Microbe 9(4), 331-341 (2011).
92. Ghosh J, Bose M, Roy S, Bhattacharyya SN. Leishmania donovani targets Dicer1 to downregulate miR-122, lower serum cholesterol, and facilitate murine liver infection. Cell Host Microbe 13(3), 277-288 (2013).
93. Faria MS, Reis FC, Azevedo-Pereira RL, Morrison LS, Mottram JC, Lima AP. Leishmania inhibitor of serine peptidase 2 prevents TLR4 activation by neutrophil elastase promoting parasite survival in murine macrophages. J. Immunol. 186(1), 411-422 (2011).
94. Jain R, Ghoshal A, Mandal C, Shaha C. Leishmania cell surface prohibitin: role in host-parasite interaction. Cell. Microbiol. 12(4), 432-452 (2010).
95. Alvarez-Rueda N, Biron M, Le Pape P. Infectivity of Leishmania mexicana is associated with differential expression of protein kinase C-like triggered during a cell-cell contact. PLoS ONE 4(10), e7581 (2009).
96. Pillai AB, Xu W, Zhang O, Zhang K. Sphingolipid degradation in Leishmania (Leishmania) amazonensis. PLoS Negl. Trop. Dis. 6(12), e1944 (2012).
97. Nandan D, Tran T, Trinh E, Silverman JM, Lopez M. Identification of Leishmania fructose-1,6-bisphosphate aldolase as a novel activator of host macrophage Src homology 2 domain containing protein tyrosine phosphatase SHP-1. Biochem. Biophys. Res. Commun. 364(3), 601-607 (2007).
98. Sansom FM, Tang L, Ralton JE, Saunders EC, Naderer T, Mcconville MJ. Leishmania major methionine sulfoxide reductase A is required for resistance to oxidative stress and efficient replication in macrophages. PLoS ONE 8(2), e56064 (2013).
99. Manhas R, Anand S, Tripathi P, Madhubala R. Deletion of Vitamin C biosynthesis enzyme, Arabino-1, 4-lactone oxidase in Leishmania donovani results in increased pro-inflammatory responses from host immune cells. Mol. Microbiol. 91(6), 1227-1239 (2014).
100. Kima PE, Bonilla JA, Cho E et al. Identification of Leishmania proteins preferentially released in infected cells using change mediated antigen technology (CMAT). PLoS Negl. Trop. Dis. 4(10), (2010).
101. Singh N, Bajpai S, Kumar V, Gour JK, Singh RK. Identification and functional characterization of Leishmania donovani secretory peroxidase: delineating its role in NRAMP1 regulation. PLoS ONE 8(1), e53442 (2013).
102. Abu-Dayyeh I, Hassani K, Westra ER, Mottram JC, Olivier M. Comparative study of the ability of Leishmania mexicana promastigotes and amastigotes to alter macrophage signaling and functions. Infect. Immun. 78(6), 2438-2445 (2010).
103. Kamir D, Zierow S, Leng L et al. A Leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses. J. Immunol. 180(12), 8250-8261 (2008).
104. Silverman JM, Reiner NE. Exosomes and other microvesicles in infection biology: organelles with unanticipated phenotypes. Cell. Microbiol. 13(1), 1-9 (2011).
105. Silverman JM, Clos J, De'oliveira CC et al. An exosom.e-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages. J. Cell Sci. 123(Pt 6), 842-852 (2010).
106. Lambertz U, Silverman JM, Nandan D et al. Secreted virulence factors and immune evasion in visceral leishmaniasis. J. Leukoc. Biol. 91(6), 887-899 (2012).
107. Hassani K, Antoniak E, Jardim A, Olivier M. Temperature-induced protein secretion by Leishmania mexicana modulates macrophage signalling and function. PLoS ONE 6(5), e18724 (2011).