IL-4Ralpha responsiveness of non-CD4 T cells contributes to resistance in schistosoma mansoni infection in pan-T cell-specific IL-4Ralpha-deficient mice.
Dewals, Benjamin G; Hoving, Jennifer C; Leeto, Mosiuoaet al.
2009 • In American Journal of Pathology, 175 (2), p. 706-16
[en] Interleukin (IL)-4 and IL-13 are T helper 2 cytokines whose biological functions are induced through a common IL-4 receptor alpha chain (IL-4Ralpha). CD4(+) T cell-specific IL-4Ralpha-mediated signaling drives susceptibility to Leishmania major infection, but is not essential to host survival following Schistosoma mansoni infection. Here we generated a novel mouse model lacking IL-4Ralpha expression specifically on all T cells (iLck(cre)Il4ra(-/lox)), which was compared with CD4(+) T cell-specific IL-4Ralpha-deficient mice (Lck(cre)Il4ra(-/lox)), to investigate the possible roles of IL-4Ralpha responsive non-CD4(+) T cells during either L. major or S. mansoni infection. Our results demonstrate a successful generation of transgene-bearing hemizygous iLck(cre)Il4ra(-/lox) BALB/c mice that have effective deletion of IL-4Ralpha on all T-cell populations. We show that iLck(cre)Il4ra(-/lox) mice infected with L. major developed a healing disease phenotype as previously observed in Lck(cre)Il4ra(-/lox) mice, demonstrating that absence of IL-4Ralpha-responsive non-CD4(+) in addition to CD4(+) T cells does not further affect transformation of BALB/c to a healer phenotype. In acute schistosomiasis, however, iLck(cre)Il4ra(-/lox) mice showed enhanced mortality compared with Il4ra(-/lox) and Lck(cre)Il4ra(-/lox) mice. iLck(cre)Il4ra(-/lox) mice died with similar kinetics to highly susceptible Il4ra(-/-) mice, despite controlling gut inflammation. In addition, iLck(cre)Il4ra(-/lox) mice presented increased liver granuloma sizes, as compared with Lck(cre)Il4ra(-/lox) mice, with similar eosinophils, fibrosis, and liver damage. In conclusion, IL-4Ralpha-responsive non-CD4(+) T cells prolong survival to acute schistosomiasis and contribute to the better control of hepatic granulomatous inflammation.
Disciplines :
Immunology & infectious disease
Author, co-author :
Dewals, Benjamin G ; Université de Liège - ULiège > Immunologie et vaccinologie
Hoving, Jennifer C; University of Cape Town > Immunology Division
Leeto, Mosiuoa; University of Cape Town > Division Immunology
Marillier, Reece G; University of Cape Town > Divivsion Immunology
Govender, Umeshree; University of Cape Town > Division Immunology
Cutler, Antony J; University of Cape Town > Division Immunology
Horsnell, William G C; University of Cape Town > Division Immunology
Brombacher, Frank; University of Cape Town > Division Immunology
Language :
English
Title :
IL-4Ralpha responsiveness of non-CD4 T cells contributes to resistance in schistosoma mansoni infection in pan-T cell-specific IL-4Ralpha-deficient mice.
Publication date :
2009
Journal title :
American Journal of Pathology
ISSN :
0002-9440
eISSN :
1525-2191
Publisher :
American Society for Investigative Pathology, Bethesda, United States - Maryland
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