Microbiota regulate the ability of lung dendritic cells to induce IgA class-switch recombination and generate protective gastrointestinal immune responses

Journal of Experimental Medicine

Volumn 213, Issue 1, 2016, Pages 53-73

  Ruane, Darren ^a,b   Chorny, Alejo ^b   Lee, Haekyung ^a,b   Faith, Jeremiah ^b   Pandey, Gaurav ^b   Shan, Meimei ^b   Simchoni, Noa ^b   Rahman, Adeeb ^b   Garg, Aakash ^a   Weinstein, Erica G ^b   Oropallo, Michael ^b   Gaylord, Michelle ^a,b   Ungaro, Ryan ^a   Cunningham Rundles, Charlotte ^b   Alexandropoulos, Konstantina ^b   Mucida, Daniel ^c   Merad, Miriam ^b   Cerutti, Andrea ^b   Mehandru, Saurabh ^a,b  

^a Division of Gastroenterology   (United States)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^c ROCKEFELLER UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; ALPHA4BETA7 RECEPTOR; AMPICILLIN; APRIL PROTEIN; B CELL ACTIVATING FACTOR; CARBOXYFLUORESCEIN DIACETATE SUCCINIMIDYL ESTER; CD103 ANTIGEN; CD11B ANTIGEN; CD24 ANTIGEN; CD64 ANTIGEN; CHEMOKINE RECEPTOR CCR9; CHOLERA TOXIN; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; INTERLEUKIN 10; LYMPHOCYTE ANTIGEN RECEPTOR; METRONIDAZOLE; MYELOID DIFFERENTIATION FACTOR 88; NEOMYCIN; RETINOIC ACID; TOLL LIKE RECEPTOR ADAPTOR MOLECULE 1; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; VANCOMYCIN; ALPHA E INTEGRINS; ALPHA INTEGRIN; CC CHEMOKINE RECEPTOR 9; CHEMOKINE RECEPTOR CCR; INTEGRIN; INTEGRIN ALPHA4BETA7; LEUKOCYTE ANTIGEN; TICAM-1 PROTEIN, MOUSE; VESICULAR TRANSPORT ADAPTOR PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN PRESENTING CELL; ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; CELL MIGRATION; CLASS SWITCH RECOMBINATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITIC CELL; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GASTROINTESTINAL IMMUNE RESPONSE; GERMFREE MOUSE; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOGLOBULIN PRODUCTION; IMMUNOHISTOCHEMISTRY; LAMINA PROPRIA; LUNG ALVEOLUS CELL; MACROPHAGE; MICROFLORA; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; ANIMAL; CELL MOTION; DRUG EFFECTS; GASTROINTESTINAL TRACT; GENE EXPRESSION; GENE REARRANGEMENT; GENETICS; IMMUNOLOGY; LUNG; LUNG ALVEOLUS MACROPHAGE; METABOLISM; MICROBIOLOGY;

ADAPTOR PROTEINS, VESICULAR TRANSPORT; ANIMALS; ANTIGENS, CD; ANTIGENS, CD24; B-CELL ACTIVATING FACTOR; B-LYMPHOCYTES; CELL MOVEMENT; DENDRITIC CELLS; GASTROINTESTINAL TRACT; GENE EXPRESSION; IMMUNOGLOBULIN A; IMMUNOGLOBULIN CLASS SWITCHING; INTEGRIN ALPHA CHAINS; INTEGRINS; LUNG; MACROPHAGES, ALVEOLAR; MICE; MICROBIOTA; MYELOID DIFFERENTIATION FACTOR 88; RECEPTORS, CCR; TRANSFORMING GROWTH FACTOR BETA; TRETINOIN; TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 13;

EID: 84961155452     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20150567     Document Type: Article

References (96)

1. Annes, J.P., J.S. Munger, and D.B. Rifkin. 2003. Making sense of latent TGFβ activation. J. Cell Sci. 116:217-224. http ://dx.doi.org /10.1242 /jcs.00229
2. Barfod, K.K., M. Roggenbuck, L.H. Hansen, S. Schjørring, S.T. Larsen, S.J. Sørensen, and K.A. Krogfelt. 2013. The murine lung microbiome in relation to the intestinal and vaginal bacterial communities. BMC Microbiol. 13:303. http ://dx.doi.org /10.1186 /1471 -2180 -13 -303
3. Bienenstock, J., M. McDermott, D. Befus, and M. O'Neill. 1978. A common mucosal immunologic system involving the bronchus, breast and bowel. Adv. Exp. Med. Biol. 107:53-59. http ://dx.doi.org /10.1007 /978 -1 -4684 -3369 -2 _7
4. Bishop, G.A., and B.S. Hostager. 2001. B lymphocyte activation by contactmediated interactions with T lymphocytes. Curr. Opin. Immunol. 13:278-285. http ://dx.doi.org /10.1016 /S0952 -7915(00)00216 -8
5. Bollinger, R.R., M.L. Everett, S.D. Wahl, Y.H. Lee, P.E. Orndorff, and W. Parker. 2006. Secretory IgA and mucin-mediated biofilm formation by environmental strains of Escherichia coli: role of type 1 pili. Mol. Immunol. 43:378-387. http ://dx.doi.org /10.1016 /j.molimm.2005.02.013
6. Casola, S., K.L. Otipoby, M. Alimzhanov, S. Humme, N. Uyttersprot, J.L. Kutok, M.C. Carroll, and K. Rajewsky. 2004. B cell receptor signal strength determines B cell fate. Nat. Immunol. 5:317-327. http ://dx.doi .org /10.1038 /ni1036
7. Cerutti, A. 2008. The regulation of IgA class switching. Nat. Rev. Immunol. 8:421-434. http ://dx.doi.org /10.1038 /nri2322
8. Cerutti, A., and M. Rescigno. 2008. The biology of intestinal immunoglobulin A responses. Immunity. 28:740-750. http ://dx.doi.org /10.1016 /j .immuni.2008.05.001
9. Cerutti, A., X. Qiao, and B. He. 2005. Plasmacytoid dendritic cells and the regulation of immunoglobulin heavy chain class switching. Immunol. Cell Biol. 83:554-562. http ://dx.doi.org /10.1111 /j.1440 -1711.2005.01389.x
10. Chaudhuri, J., and F.W. Alt. 2004. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat. Rev. Immunol. 4:541-552. http ://dx.doi.org /10.1038 /nri1395
11. Choi, Y.S., and N. Baumgarth. 2008. Dual role for B-1a cells in immunity to influenza virus infection. J. Exp. Med. 205:3053-3064. http ://dx.doi.org /10.1084 /jem.20080979
12. Cunningham-Rundles, C. 2001. Physiology of IgA and IgA deficiency. J. Clin. Immunol. 21:303-309. http ://dx.doi.org /10.1023 /A :1012241117984
13. Dullaers, M., D. Li, Y. Xue, L. Ni, I. Gayet, R. Morita, H. Ueno, K.A. Palucka, J. Banchereau, and S. Oh. 2009. A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts. Immunity. 30:120-129. http ://dx.doi.org /10.1016 /j .immuni.2008.11.008
14. Favre, L., F. Spertini, and B. Corthésy. 2005. Secretory IgA possesses intrinsic modulatory properties stimulating mucosal and systemic immune responses. J. Immunol. 175:2793-2800. http ://dx.doi.org /10.4049 / jimmunol.175.5.2793
15. Geissmann, F., P. Launay, B. Pasquier, Y. Lepelletier, M. Leborgne, A. Lehuen, N. Brousse, and R.C. Monteiro. 2001. A subset of human dendritic cells expresses IgA Fc receptor (CD89), which mediates internalization and activation upon cross-linking by IgA complexes. J. Immunol. 166:346-352. http ://dx.doi.org /10.4049 /jimmunol.166.1.346
16. + DCs. J. Exp. Med. 206:3115-3130. http :// dx.doi.org /10.1084 /jem.20091756
17. + regulatory T cells. Blood. 115:1958-1968. http ://dx.doi.org /10.1182 /blood -2009-09 -245274
18. Hahne, M., T. Kataoka, M. Schröter, K. Hofmann, M. Irmler, J.L. Bodmer, P. Schneider, T. Bornand, N. Holler, L.E. French, et al. 1998. APR IL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J. Exp. Med. 188:1185-1190. http ://dx.doi.org /10.1084 /jem.188.6.1185
19. Haimila, K., E. Einarsdottir, A. de Kauwe, L.L. Koskinen, Q. Pan-Hammarström, T. Kaartinen, K. Kurppa, F. Ziberna, T. Not, S. Vatta, et al. 2009. The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. Genes Immun. 10:151-161. http ://dx.doi.org /10.1038 /gene.2008.89
20. Harriman, G.R., M. Bogue, P. Rogers, M. Finegold, S. Pacheco, A. Bradley, Y. Zhang, and I.N. Mbawuike. 1999. Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes. J. Immunol. 162:2521-2529.
21. He, B., W. Xu, P.A. Santini, A.D. Polydorides, A. Chiu, J. Estrella, M. Shan, A. Chadburn, V. Villanacci, A. Plebani, et al. 2007. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APR IL. Immunity. 26:812-826. http ://dx.doi.org /10.1016 /j.immuni.2007.04.014
22. He, B., R. Santamaria, W. Xu, M. Cols, K. Chen, I. Puga, M. Shan, H. Xiong, J.B. Bussel, A. Chiu, et al. 2010. The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nat. Immunol. 11:836-845. http ://dx.doi.org /10 .1038 /ni.1914
23. + dendritic cells are protected from influenza virus infection. J. Clin. Invest. 122:4037-4047. http ://dx.doi.org /10.1172 / JCI60659
24. Heng, T.S., and M.W. Painter. Immunological Genome Project Consortium. 2008. The Immunological Genome Project: networks of gene expression in immune cells. Nat. Immunol. 9:1091-1094. http ://dx.doi.org /10.1038 /ni1008 -1091
25. + dendritic cells in cytotoxic T cell immunity. Science. 322:1097-1100. http ://dx.doi.org /10.1126 /science.1164206
26. Hill, D.A., and D. Artis. 2010. Intestinal bacteria and the regulation of immune cell homeostasis. Annu. Rev. Immunol. 28:623-667. http://dx.doi.org/10.1146 /annurev-immunol-030409-101330
27. Huang, W., B.T. Sherman, and R.A. Lempicki. 2009. Systematic and integrative analysis of large gene lists using DAV ID bioinformatics resources. Nat. Protoc. 4:44-57. http ://dx.doi.org /10.1038 /nprot.2008.211
28. Huang, Y.J., E.S. Charlson, R.G. Collman, S. Colombini-Hatch, F.D. Martinez, and R.M. Senior. 2013. The role of the lung microbiome in health and disease. A National Heart, Lung, and Blood Institute workshop report. Am. J. Respir. Crit. Care Med. 187:1382-1387. http ://dx.doi.org /10.1164/rccm.201303 -0488WS
29. Ichinohe, T., I.K. Pang, Y. Kumamoto, D.R. Peaper, J.H. Ho, T.S. Murray, and A. Iwasaki. 2011. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. USA. 108:5354-5359. http ://dx.doi.org /10.1073 /pnas.1019378108
30. Ing, R., M. Segura, N. Thawani, M. Tam, and M.M. Stevenson. 2006. Interaction of mouse dendritic cells and malaria-infected erythrocytes:uptake, maturation, and antigen presentation. J. Immunol. 176:441-450. http ://dx.doi.org /10.4049 /jimmunol.176.1.441
31. Iwasaki, A., and B.L. Kelsall. 1999. Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells. J. Exp. Med. 190:229-239. http ://dx.doi.org /10.1084 /jem.190.2.229
32. Jacob, C.M., A.C. Pastorino, K. Fahl, M. Carneiro-Sampaio, and R.C. Monteiro. 2008. Autoimmunity in IgA deficiency: revisiting the role of IgA as a silent housekeeper. J. Clin. Immunol. 28(S1, Suppl 1):S56-S61. http ://dx.doi.org /10.1007 /s10875 -007 -9163 -2
33. Jacob, J., G. Kelsoe, K. Rajewsky, and U. Weiss. 1991. Intraclonal generation of antibody mutants in germinal centres. Nature. 354:389-392. http ://dx .doi.org /10.1038 /354389a0
34. Kawasaki, A., N. Tsuchiya, J. Ohashi, Y. Murakami, T. Fukazawa, M. Kusaoi, S. Morimoto, K. Matsuta, H. Hashimoto, Y. Takasaki, and K. Tokunaga. 2007. Role of APR IL (TNF SF13) polymorphisms in the susceptibility to systemic lupus erythematosus in Japanese. Rheumatology (Oxford). 46:776-782. http ://dx.doi.org /10.1093 /rheumatology /kem019
35. Kim, S.V., W.V. Xiang, C. Kwak, Y. Yang, X.W. Lin, M. Ota, U. Sarpel, D.B. Rifkin, R. Xu, and D.R. Littman. 2013. GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science. 340:1456-1459. http ://dx.doi.org /10.1126 /science.1237013
36. Langford, T.D., M.P. Housley, M. Boes, J. Chen, M.F. Kagnoff, F.D. Gillin, and L. Eckmann. 2002. Central importance of immunoglobulin A in host defense against Giardia spp. Infect. Immun. 70:11-18. http ://dx.doi.org /10.1128 /IAI.70.1.11 -18.2002
37. Langlet, C., S. Tamoutounour, S. Henri, H. Luche, L. Ardouin, C. Grégoire, B. Malissen, and M. Guilliams. 2012. CD64 expression distinguishes monocyte-derived and conventional dendritic cells and reveals their distinct role during intramuscular immunization. J. Immunol. 188:1751-1760. http ://dx.doi.org /10.4049 /jimmunol.1102744
38. Litinskiy, M.B., B. Nardelli, D.M. Hilbert, B. He, A. Schaffer, P. Casali, and A. Cerutti. 2002. DCs induce CD40-independent immunoglobulin class switching through BLyS and APR IL. Nat. Immunol. 3:822-829. http :// dx.doi.org /10.1038 /ni829
39. Liu, Y.J., F. Malisan, O. de Bouteiller, C. Guret, S. Lebecque, J. Banchereau, F.C. Mills, E.E. Max, and H. Martinez-Valdez. 1996. Within germinal centers, isotype switching of immunoglobulin genes occurs after the onset of somatic mutation. Immunity. 4:241-250. http ://dx.doi.org /10.1016 /S1074 -7613(00)80432 -X
40. Macpherson, A.J., and T. Uhr. 2004. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 303:1662-1665. http ://dx.doi.org /10.1126 /science.1091334
41. Macpherson, A.J., D. Gatto, E. Sainsbury, G.R. Harriman, H. Hengartner, and R.M. Zinkernagel. 2000. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science. 288:2222-2226. http ://dx.doi.org /10.1126 /science.288.5474.2222
42. Mantis, N.J., M.C. Cheung, K.R. Chintalacharuvu, J. Rey, B. Corthésy, and M.R. Neutra. 2002. Selective adherence of IgA to murine Peyer's patch M cells: evidence for a novel IgA receptor. J. Immunol. 169:1844-1851. http ://dx.doi.org /10.4049 /jimmunol.169.4.1844
43. Martinoli, C., A. Chiavelli, and M. Rescigno. 2007. Entry route of Salmonella typhimurium directs the type of induced immune response. Immunity. 27:975-984. http ://dx.doi.org /10.1016 /j.immuni.2007.10.011
44. Mazanec, M.B., J.G. Nedrud, C.S. Kaetzel, and M.E. Lamm. 1993. A threetiered view of the role of IgA in mucosal defense. Immunol. Today. 14:430-435. http ://dx.doi.org /10.1016 /0167 -5699(93)90245 -G
45. Moore, P.A., O. Belvedere, A. Orr, K. Pieri, D.W. LaFleur, P. Feng, D. Soppet, M. Charters, R. Gentz, D. Parmelee, et al. 1999. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 285:260-263. http ://dx.doi.org /10.1126 /science.285.5425.260
46. Mora, J.R., M.R. Bono, N. Manjunath, W. Weninger, L.L. Cavanagh, M. Rosemblatt, and U.H. Von Andrian. 2003. Selective imprinting of guthoming T cells by Peyer's patch dendritic cells. Nature. 424:88-93. http ://dx.doi.org /10.1038 /nature01726
47. Mora, J.R., M. Iwata, B. Eksteen, S.Y. Song, T. Junt, B. Senman, K.L. Otipoby, A. Yokota, H. Takeuchi, P. Ricciardi-Castagnoli, et al. 2006. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science. 314:1157-1160. http ://dx.doi.org /10.1126 /science.1132742
48. Mucida, D., Y. Park, G. Kim, O. Turovskaya, I. Scott, M. Kronenberg, and H. Cheroutre. 2007. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science. 317:256-260. http ://dx.doi.org /10.1126 /science.1145697
49. Muramatsu, M., K. Kinoshita, S. Fagarasan, S. Yamada, Y. Shinkai, and T. Honjo. 2000. Class switch recombination and hypermutation require activationinduced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 102:553-563. http ://dx.doi.org /10.1016 /S0092 -8674(00)00078 -7
50. Naik, S., N. Bouladoux, C. Wilhelm, M.J. Molloy, R. Salcedo, W. Kastenmuller, C. Deming, M. Quinones, L. Koo, S. Conlan, et al. 2012. Compartmentalized control of skin immunity by resident commensals. Science. 337:1115-1119. http ://dx.doi.org /10.1126 /science.1225152
51. Naito, T., T. Suda, K. Suzuki, Y. Nakamura, N. Inui, J. Sato, K. Chida, and H. Nakamura. 2008. Lung dendritic cells have a potent capability to induce production of immunoglobulin A. Am. J. Respir. Cell Mol. Biol. 38:161-167. http ://dx.doi.org /10.1165 /rcmb.2007 -0237OC
52. Nardelli, B., O. Belvedere, V. Roschke, P.A. Moore, H.S. Olsen, T.S. Migone, S. Sosnovtseva, J.A. Carrell, P. Feng, J.G. Giri, and D.M. Hilbert. 2001. Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood. 97:198-204. http ://dx.doi.org /10.1182 /blood.V97.1.198
53. Nimmerjahn, F., and J.V. Ravetch. 2006. Fcgamma receptors: old friends and new family members. Immunity. 24:19-28. http ://dx.doi.org /10.1016 /j .immuni.2005.11.010
54. Nonoyama, S., D. Hollenbaugh, A. Aruffo, J.A. Ledbetter, and H.D. Ochs. 1993. B cell activation via CD40 is required for specific antibody production by antigen-stimulated human B cells. J. Exp. Med. 178:1097-1102. http ://dx.doi.org /10.1084 /jem.178.3.1097
55. Noverr, M.C., N.R. Falkowski, R.A. McDonald, A.N. McKenzie, and G.B. Huffnagle. 2005. Development of allergic airway disease in mice following antibiotic therapy and fungal microbiota increase: role of host genetics, antigen, and interleukin-13. Infect. Immun. 73:30-38. http ://dx .doi.org /10.1128 /IAI.73.1.30 -38.2005
56. O'Neill, L.A., D. Golenbock, and A.G. Bowie. 2013. The history of Toll-like receptors - redefining innate immunity. Nat. Rev. Immunol. 13:453-460. http ://dx.doi.org /10.1038 /nri3446
57. Oh, J.Z., R. Ravindran, B. Chassaing, F.A. Carvalho, M.S. Maddur, M. Bower, P. Hakimpour, K.P. Gill, H.I. Nakaya, F. Yarovinsky, et al. 2014. TLR5- mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity. 41:478-492. http ://dx.doi .org /10.1016 /j.immuni.2014.08.009
58. Olszak, T., D. An, S. Zeissig, M.P. Vera, J. Richter, A. Franke, J.N. Glickman, R. Siebert, R.M. Baron, D.L. Kasper, and R.S. Blumberg. 2012. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 336:489-493. http ://dx.doi.org /10.1126 /science.1219328
59. Peterson, D.A., N.P. McNulty, J.L. Guruge, and J.I. Gordon. 2007. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe. 2:328-339. http ://dx.doi.org /10.1016 /j.chom.2007.09.013
60. Phalipon, A., and B. Corthésy. 2003. Novel functions of the polymeric Ig receptor: well beyond transport of immunoglobulins. Trends Immunol. 24:55-58. http ://dx.doi.org /10.1016 /S1471 -4906(02)00031 -5
61. Pilette, C., B. Detry, A. Guisset, J. Gabriels, and Y. Sibille. 2010. Induction of interleukin-10 expression through Fcα receptor in human monocytes and monocyte-derived dendritic cells: role of p38 MAPKinase. Immunol. Cell Biol. 88:486-493. http ://dx.doi.org /10.1038 /icb.2009.120
62. Quezada, S.A., L.Z. Jarvinen, E.F. Lind, and R.J. Noelle. 2004. CD40/CD154 interactions at the interface of tolerance and immunity. Annu. Rev. Immunol. 22:307-328. http ://dx.doi.org /10.1146 /annurev.immunol.22.012703.104533
63. Ridaura, V.K., J.J. Faith, F.E. Rey, J. Cheng, A.E. Duncan, A.L. Kau, N.W. Griffin, V. Lombard, B. Henrissat, J.R. Bain, et al. 2013. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 341:1241214. http ://dx.doi.org /10.1126 /science.1241214
64. Rimoldi, M., M. Chieppa, V. Salucci, F. Avogadri, A. Sonzogni, G.M. Sampietro, A. Nespoli, G. Viale, P. Allavena, and M. Rescigno. 2005. Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat. Immunol. 6:507-514. http ://dx .doi.org /10.1038 /ni1192
65. Robinson, M.D., D.J. McCarthy, and G.K. Smyth. 2010. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 26:139-140. http ://dx.doi.org /10.1093 / bioinformatics /btp616
66. Rodríguez, A., A. Tjärnlund, J. Ivanji, M. Singh, I. García, A. Williams, P.D. Marsh, M. Troye-Blomberg, and C. Fernández. 2005. Role of IgA in the defense against respiratory infections IgA deficient mice exhibited increased susceptibility to intranasal infection with Mycobacterium bovis BCG. Vaccine. 23:2565-2572.
67. Ruane, D., L. Brane, B.S. Reis, C. Cheong, J. Poles, Y. Do, H. Zhu, K. Velinzon, J.H. Choi, N. Studt, et al. 2013. Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract. J. Exp. Med. 210:1871-1888. http ://dx.doi.org /10.1084 /jem.20122762
68. Russell, S.L., M.J. Gold, M. Hartmann, B.P. Willing, L. Thorson, M. Wlodarska, N. Gill, M.R. Blanchet, W.W. Mohn, K.M. McNagny, and B.B. Finlay. 2012. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep. 13:440-447. http ://dx.doi.org /10.1038 /embor.2012.32
69. Russell, S.L., M.J. Gold, B.P. Willing, L. Thorson, K.M. McNagny, and B.B. Finlay. 2013. Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma. Gut Microbes. 4:158-164. http :// dx.doi.org /10.4161 /gmic.23567
70. + T cell-dependent immunoglobulin A response to influenza infection in the absence of key cognate T-B interactions. J. Exp. Med. 198:1011-1021. http ://dx.doi.org /10.1084 / jem.20021745
71. + Peyer's patch dendritic cells secrete IL-6 and induce IgA secretion from naive B cells. J. Immunol. 171:3684-3690. http ://dx.doi .org /10.4049 /jimmunol.171.7.3684
72. Schlissel, M.S. 2003. Regulating antigen-receptor gene assembly. Nat. Rev. Immunol. 3:890-899. http ://dx.doi.org /10.1038 /nri1225
73. + dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity. 38:970-983. http ://dx.doi.org /10.1016 /j .immuni.2013.04.011
74. Schneider, P., F. MacKay, V. Steiner, K. Hofmann, J.L. Bodmer, N. Holler, C. Ambrose, P. Lawton, S. Bixler, H. Acha-Orbea, et al. 1999. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J. Exp. Med. 189:1747-1756. http ://dx.doi.org /10.1084 /jem.189.11.1747
75. Sealy, R., S. Surman, J.L. Hurwitz, and C. Coleclough. 2003. Antibody response to influenza infection of mice: different patterns for glycoprotein and nucleocapsid antigens. Immunology. 108:431-439. http ://dx.doi.org /10 .1046 /j.1365 -2567.2003.01615.x
76. Seo, G.Y., Y.S. Jang, H.A. Kim, M.R. Lee, M.H. Park, S.R. Park, J.M. Lee, J. Choe, and P.H. Kim. 2013. Retinoic acid, acting as a highly specific IgA isotype switch factor, cooperates with TGF-β1 to enhance the overall IgA response. J. Leukoc. Biol. 94:325-335. http ://dx.doi.org /10.1189 / jlb.0313128
77. Silvey, K.J., A.B. Hutchings, M. Vajdy, M.M. Petzke, and M.R. Neutra. 2001. Role of immunoglobulin A in protection against reovirus entry into murine Peyer's patches. J. Virol. 75:10870-10879. http ://dx.doi.org /10.1128 /JVI.75.22.10870 -10879.2001
78. + T cells in immunity to infection by the attaching and effacing pathogen Citrobacter rodentium. Infect. Immun. 71:5077-5086. http ://dx.doi.org /10.1128 /IAI.71.9.5077 -5086.2003
79. Spangler, B.D. 1992. Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol. Rev. 56:622-647.
80. Stavnezer, J. 1996. Antibody class switching. Adv. Immunol. 61:79-146. http :// dx.doi.org /10.1016 /S0065 -2776(08)60866 -4
81. Stavnezer, J., J.E. Guikema, and C.E. Schrader. 2008. Mechanism and regulation of class switch recombination. Annu. Rev. Immunol. 26:261-292. http ://dx.doi.org /10.1146 /annurev.immunol.26.021607.090248
82. Stohl, W., S. Metyas, S.M. Tan, G.S. Cheema, B. Oamar, V. Roschke, Y. Wu, K.P. Baker, and D.M. Hilbert. 2004. Inverse association between circulating APR IL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann. Rheum. Dis. 63:1096-1103. http :// dx.doi.org /10.1136 /ard.2003.018663
83. Storey, J.D., and R. Tibshirani. 2003. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA. 100:9440-9445. http ://dx.doi.org /10 .1073 /pnas.1530509100
84. Sun, K., F.E. Johansen, L. Eckmann, and D.W. Metzger. 2004. An important role for polymeric Ig receptor-mediated transport of IgA in protection against Streptococcus pneumoniae nasopharyngeal carriage. J. Immunol. 173:4576-4581. http ://dx.doi.org /10.4049 /jimmunol.173.7.4576
85. + lung dendritic cells in vitro. Am. J. Respir. Cell Mol. Biol. 46:773-780. http ://dx.doi.org /10.1165 /rcmb.2011 -0329OC
86. Tezuka, H., Y. Abe, M. Iwata, H. Takeuchi, H. Ishikawa, M. Matsushita, T. Shiohara, S. Akira, and T. Ohteki. 2007. Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature. 448:929-933. http ://dx.doi.org /10.1038 /nature06033
87. Tokuhara, D., Y. Yuki, T. Nochi, T. Kodama, M. Mejima, S. Kurokawa, Y. Takahashi, M. Nanno, U. Nakanishi, F. Takaiwa, et al. 2010. Secretory IgA-mediated protection against V. cholerae and heat-labile enterotoxinproducing enterotoxigenic Escherichia coli by rice-based vaccine. Proc. Natl. Acad. Sci. USA. 107:8794-8799. http ://dx.doi.org /10.1073 /pnas .0914121107
88. Tsuji, M., K. Suzuki, H. Kitamura, M. Maruya, K. Kinoshita, I.I. Ivanov, K. Itoh, D.R. Littman, and S. Fagarasan. 2008. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity. 29:261-271. http :// dx.doi.org /10.1016 /j.immuni.2008.05.014
89. Tusher, V.G., R. Tibshirani, and G. Chu. 2001. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. USA. 98:5116-5121. http ://dx.doi.org /10.1073 /pnas.091062498
90. Vermaelen, K.Y., I. Carro-Muino, B.N. Lambrecht, and R.A. Pauwels. 2001. Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes. J. Exp. Med. 193:51-60. http ://dx .doi.org /10.1084 /jem.193.1.51
91. Villablanca, E.J., B. Cassani, U.H. von Andrian, and J.R. Mora. 2011. Blocking lymphocyte localization to the gastrointestinal mucosa as a therapeutic strategy for inflammatory bowel diseases. Gastroenterology. 140:1776-1784. http ://dx.doi.org /10.1053 /j.gastro.2011.02.015
92. Way, S.S., A.C. Borczuk, and M.B. Goldberg. 1999. Adaptive immune response to Shigella flexneri 2a cydC in immunocompetent mice and mice lacking immunoglobulin A. Infect. Immun. 67:2001-2004.
93. Wilkes, D.S., and J.C. Weissler. 1994. Alloantigen-induced immunoglobulin production in human lung: differential effects of accessory cell populations on IgG synthesis. Am. J. Respir. Cell Mol. Biol. 10:339-346. http ://dx.doi.org /10.1165 /ajrcmb.10.3.8117452
94. Wortis, H.H., M. Teutsch, M. Higer, J. Zheng, and D.C. Parker. 1995. B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes. Proc. Natl. Acad. Sci. USA. 92:3348-3352. http ://dx.doi.org /10.1073 / pnas.92.8.3348
95. Xu, W., B. He, A. Chiu, A. Chadburn, M. Shan, M. Buldys, A. Ding, D.M. Knowles, P.A. Santini, and A. Cerutti. 2007. Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI. Nat. Immunol. 8:294-303. http ://dx.doi.org /10.1038 /ni1434
96. Xu, W., P.A. Santini, A.J. Matthews, A. Chiu, A. Plebani, B. He, K. Chen, and A. Cerutti. 2008. Viral double-stranded RNA triggers Ig class switching by activating upper respiratory mucosa B cells through an innate TLR3 pathway involving BAFF. J. Immunol. 181:276-287. http ://dx.doi.org /10 .4049 /jimmunol.181.1.276