IL-4Ralpha-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection.

[en] In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Ralpha and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Ralpha(-)/(-) mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Ralpha expressing B cells into naive BALB/c mice, but not IL-4Ralpha or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4(+) T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88(-)/(-) B cells. These data suggest TLR dependent antigen processing by IL-4Ralpha-responsive B cells producing IL-13 contribute significantly to CD4(+) T cell-mediated protective immunity against N. brasiliensis infection.

Disciplines :

Immunology & infectious disease

Author, co-author :

Horsnell, William G. C.

Darby, Matthew G.

Hoving, Jennifer C.

Nieuwenhuizen, Natalie

McSorley, Henry J.

Ndlovu, Hlumani

Bobat, Saeeda

Kimberg, Matti

Kirstein, Frank

Cutler, Anthony J.

More authors (3 more)

Language :

English

Title :

IL-4Ralpha-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection.

Publication date :

October 2013

Journal title :

PLoS Pathogens

ISSN :

1553-7366

eISSN :

1553-7374

Publisher :

Public Library of Science, United States - California

Volume :

Issue :

Pages :

e1003662

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 19 December 2013

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Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, et al. (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118: 1311-1321.
Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, et al. (2006) Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 367: 1521-1532.
Hotez PJ, (2007) Hookworm and Poverty. Ann N Y Acad Sci 1136: 38-44.
Jardim-Botelho A, Raff S, Rodrigues Rde A, Hoffman HJ, Diemert DJ, et al. (2008) Hookworm, Ascaris lumbricoides infection and polyparasitism associated with poor cognitive performance in Brazilian schoolchildren. Trop Med Int Health 13: 994-1004.
Marsland BJ, Kurrer M, Reissmann R, Harris NL, Kopf M, (2008) Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages. Eur J Immunol 38: 479-488.
Muro A, Perez-Arellano JL, (2010) Nitric oxide and respiratory helminthic diseases. J Biomed Biotechnol 2010: 958108.
Harvie M, Camberis M, Tang SC, Delahunt B, Paul W, et al. (2010) The lung is an important site for priming CD4 T cell mediated protective immunity against gastrointestinal helminth parasites. Infect Immun 78 (9) (): 3753-62.
Wright V, Bickle Q, (2005) Immune responses following experimental human hookworm infection. Clin Exp Immunol 142: 398-403.
Turner JD, Faulkner H, Kamgno J, Cormont F, Van Snick J, et al. (2003) Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. J Infect Dis 188: 1768-1775.
Finkelman FD, Urban JF Jr, (2001) The other side of the coin: the protective role of the TH2 cytokines. J Allergy Clin Immunol 107: 772-780.
Urban JF Jr, Noben-Trauth N, Schopf L, Madden KB, Finkelman FD, (2001) Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites. J Immunol 167: 6078-6081.
Horsnell WG, Cutler AJ, Hoving JC, Mearns H, Myburgh E, et al. (2007) Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice. PLoS Pathog 3: e1.
Herbert DR, Yang JQ, Hogan SP, Groschwitz K, Khodoun M, et al. (2009) Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. J Exp Med 206: 2947-2957.
Nieuwenhuizen N, Herbert DR, Brombacher F, Lopata AL, (2009) Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by Anisakis. Allergy 64: 1309-1318.
Mearns H, Horsnell WG, Hoving JC, Dewals B, Cutler AJ, et al. (2008) Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology. Infect Immun 76: 5535-5542.
Thawer SG, Horsnell WG, Darby M, Hoving JC, Dewals B, et al. (2013) Lung-resident CD4 T cells are sufficient for IL-4Ralpha-dependent recall immunity to Nippostrongylus brasiliensis infection. Mucosal Immunol [epub ahead of print] doi:10.1038/mi.2013.40.
Anthony RM, Urban JF Jr, Alem F, Hamed HA, Rozo CT, et al. (2006) Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nat Med 12: 955-960.
Morimoto M, Whitmire J, Xiao S, Anthony RM, Mirakami H, et al. (2004) Peripheral CD4 T cells rapidly accumulate at the host: parasite interface during an inflammatory Th2 memory response. J Immunol 172: 2424-2430.
McCoy KD, Stoel M, Stettler R, Merky P, Fink K, et al. (2008) Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection. Cell Host Microbe 4: 362-373.
Liu Q, Kreider T, Bowdridge S, Liu Z, Song Y, et al. (2010) B cells have distinct roles in host protection against different nematode parasites. J Immunol 184: 5213-5223.
Wojciechowski W, Harris DP, Sprague F, Mousseau B, Makris M, et al. (2009) Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus. Immunity 30: 421-433.
Knott ML, Matthaei KI, Giacomin PR, Wang H, Foster PS, et al. (2007) Impaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis. Int J Parasitol 37: 1367-1378.
Giacomin PR, Gordon DL, Botto M, Daha MR, Sanderson SD, et al. (2008) The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode Nippostrongylus brasiliensis. Mol Immunol 45: 446-455.
Ohnmacht C, Voehringer D, (2009) Basophil effector function and homeostasis during helminth infection. Blood 113: 2816-2825.
Voehringer D, Shinkai K, Locksley RM, (2004) Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 20: 267-277.
Hoving JC, Kirstein F, Nieuwenhuizen NE, Fick LC, Hobeika E, et al. (2011) B Cells That Produce Immunoglobulin E Mediate Colitis in BALB/c Mice. Gastroenterology 142 (1) (): 96-108.
Chappell CP, Draves KE, Giltiay NV, Clark EA, (2012) Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J Exp Med 209: 1825-1840.
Flores-Langarica A, Marshall JL, Bobat S, Mohr E, Hitchcock J, et al. (2011) T-zone localized monocyte-derived dendritic cells promote Th1 priming to Salmonella. Eur J Immunol 41: 2654-2665.
Bernasconi NL, Traggiai E, Lanzavecchia A, (2002) Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298: 2199-2202.
Jellison ER, Guay HM, Szomolanyi-Tsuda E, Welsh RM, (2007) Dynamics and magnitude of virus-induced polyclonal B cell activation mediated by BCR-independent presentation of viral antigen. Eur J Immunol 37: 119-128.
Pasare C, Medzhitov R, (2005) Control of B-cell responses by Toll-like receptors. Nature 438: 364-368.
Ruprecht CR, Lanzavecchia A, (2006) Toll-like receptor stimulation as a third signal required for activation of human naive B cells. Eur J Immunol 36: 810-816.
Sayi A, Kohler E, Toller IM, Flavell RA, Muller W, et al. (2011) TLR-2-activated B cells suppress Helicobacter-induced preneoplastic gastric immunopathology by inducing T regulatory-1 cells. J Immunol 186: 878-890.
Lund FE, (2008) Cytokine-producing B lymphocytes-key regulators of immunity. Curr Opin Immunol 20: 332-338.
Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, et al. (2000) Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1: 475-482.
Harris DP, Goodrich S, Mohrs K, Mohrs M, Lund FE, (2005) Cutting edge: the development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor alpha, and Th2 cells. J Immunol 175: 7103-7107.
Bouaziz JD, Yanaba K, Tedder TF, (2008) Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev 224: 201-214.
Amu S, Saunders SP, Kronenberg M, Mangan NE, Atzberger A, et al. (2010) Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model. J Allergy Clin Immunol 125: 1114-e1118, 1114-1124, e1118.
Barr TA, Brown S, Mastroeni P, Gray D, (2009) B cell intrinsic MyD88 signals drive IFN-gamma production from T cells and control switching to IgG2c. J Immunol 183: 1005-1012.
Barr TA, Brown S, Mastroeni P, Gray D, (2010) TLR and B cell receptor signals to B cells differentially program primary and memory Th1 responses to Salmonella enterica. J Immunol 185: 2783-2789.
Morrison VL, Barr TA, Brown S, Gray D, (2010) TLR-mediated loss of CD62L focuses B cell traffic to the spleen during Salmonella typhimurium infection. J Immunol 185: 2737-2746.
Wilson MS, Taylor MD, O'Gorman MT, Balic A, Barr TA, et al. (2010) Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol 40: 1682-1696.
Cliffe LJ, Humphreys NE, Lane TE, Potten CS, Booth C, et al. (2005) Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science 308: 1463-1465.
Horsnell WG, Vira A, Kirstein F, Mearns H, Hoving JC, et al. (2010) IL-4Ralpha-responsive smooth muscle cells contribute to initiation of T(H)2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal Immunol 4 (1) (): 83-92.
Voehringer D, Reese TA, Huang X, Shinkai K, Locksley RM, (2006) Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med 203: 1435-1446.
Zhao A, Urban JF Jr, Anthony RM, Sun R, Stiltz J, et al. (2008) Th2 cytokine-induced alterations in intestinal smooth muscle function depend on alternatively activated macrophages. Gastroenterology 135: 217-e211, 217-225, e211.
Mohr E, Cunningham AF, Toellner KM, Bobat S, Coughlan RE, et al. (2010) IFN-{gamma} produced by CD8 T cells induces T-bet-dependent and-independent class switching in B cells in responses to alum-precipitated protein vaccine. Proc Natl Acad Sci U S A 107: 17292-17297.