Expression of IL-4 receptor on non-bone marrow-derived cells is necessary for the timely elimination of Strongyloides venezuelensis in mice, but not for intestinal IL-4 production.
In rodents and in humans, Strongyloides infection induces an immune response which is predominantly Th2 in nature. In an attempt to understand the role of the IL-4R/STAT6 signaling pathway, the pathway activated by the Th2 cytokines IL-4 and IL-13, in the induction of protection during Strongyloides venezuelensis infection, we have carried out experiments in mice lacking the IL-4Ralpha chain. Experiments were also carried out in STAT6 (STAT6(-/-)) and IL-12-deficient (IL-12(-/-)) mice for comparison. There was enhancement of IL-13 and abolition of IFN-gamma production in the small intestine of 7 day-infected IL-12(-/-) animals but worm elimination proceeded with very similar kinetics to those of wild-type mice. In IL-4Ralpha- or STAT6-deficient mice, there was a delay in parasite elimination and a large number of S. venezuelensis adult worms was still present in the small intestine 14 days after infection. Moreover, IgE production was completely abolished in IL-4Ralpha- or STAT6-deficient mice but tissue eosinophilia was normally induced by the parasite infection in deficient mice. Bone marrow transfer experiments showed that worm elimination occurred when a functional IL-4 receptor was present only in non-bone marrow-derived cells but not when IL-4R was only expressed in bone marrow cells. The induction of IL-4, but not IL-13, occurred independently of IL-4R. We believe these results are the first direct evidence that the mechanism responsible for the timely elimination of S. venezuelensis is dependent on the activation of IL-4R and STAT6. Moreover, a functional protective response is dependent on the expression of IL-4Ralpha on non-bone marrow-derived cells.
Negrão-Corrêa
Deborah
D
Departmento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Campus Pampulha, Belo Horizonte, MG, Brazil. denegrao@icb.ufmg.br
Pinho
Vanessa
V
Souza
Danielle G
DG
Pereira
Ana Terezinha M
AT
Fernandes
Adriana
A
Scheuermann
Karina
K
Souza
Adriano L S
AL
Teixeira
Mauro M
MM
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology; D004802:Eosinophilia; D006790:Host-Parasite Interactions; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D008174:Lung Diseases, Parasitic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010270:Parasite Egg Count; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013321:Strongyloides; D013322:Strongyloidiasis / Q000276:immunology*; D018418:Th2 Cells; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015415:Biomarkers; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma