Reference : IL-4Ralpha responsiveness of non-CD4 T cells contributes to resistance in schistosoma...
Scientific journals : Article
Human health sciences : Immunology & infectious disease
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 mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Hoving, Jennifer C mailto [>University of Cape Town > > >Immunology Division > > >]
Leeto, Mosiuoa mailto [>University of Cape Town > > >Division Immunology > > >]
Marillier, Reece G mailto [>University of Cape Town > > >Divivsion Immunology > > >]
Govender, Umeshree mailto [>University of Cape Town > > >Division Immunology > > >]
Cutler, Antony J [>University of Cape Town > > >Division Immunology > > >]
Horsnell, William G C mailto [>University of Cape Town > > >Division Immunology > > >]
Brombacher, Frank mailto [>University of Cape Town > > >Division Immunology > > >]
American Journal of Pathology
American Society for Investigative Pathology
Yes (verified by ORBi)
[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.

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