Schistosoma mansoni-infected mice show augmented hepatic fibrosis and selective inhibition of liver cytokine production after treatment with anti-NK1.1 antibodies.
Gamma interferon (IFN-gamma) plays an immunoregulatory role at different stages of the experimental Schistosoma mansoni-driven processes in mice through its ability to induce cell cytotoxicity against the parasite larvae and to reduce established hepatic fibrosis. The role of Natural Killer (NK) cells, as possible major source of IFN-gamma, has never been studied during the entire course of murine schistosomiasis. In this paper, we investigated the consequences of in vivo NK cell depletion, maintained during 17 weeks of infection, on both hepatic granuloma development and immunological parameters. We found that NK cell depletion following anti-NK1.1 monoclonal antibody (mAb) injections led to an increase of hepatic collagen content in the late stages of granuloma formation and to the diminution of interleukin 12 (IL-12) p40 and IL-7 mRNA expression in the livers. The hepatic mRNA expression of other cytokines (IFN-gamma, tumor necrosis factor alpha [TNF-alpha] and IL-4), as well as humoral and cytokine responses in sera, were not significantly different between control monoclonal antibody (CmAb) and anti-NK1.1-treated mice. Thus, we demonstrate that the anti-NK1.1 treatment might induce alterations of regulatory mechanisms, detectable at a late stage of a chronic process in immunocompetent mice.
Asseman
C
C
URA CNRS 1854, Institut Pasteur, Lille, France.
Pancré
V
V
Quatennens
B
B
Auriault
C
C
D000818:Animals; D000909:Antibodies, Helminth / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D007739:L Cells; D008099:Liver / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012333:RNA, Messenger / Q000032:analysis; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007074:Immunoglobulin G; D015851:Interleukin-7; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma