Cryptosporidium parvum-specific mucosal immune response in C57BL/6 neonatal and gamma interferon-deficient mice: role of tumor necrosis factor alpha in protection.
Both neonatal and C57BL/6 gamma interferon (IFN-gamma) knockout (C57BL/6-GKO) mice are susceptible to Cryptosporidium parvum, but the course of infection is different. Neonatal mice are able to clear the parasite within 3 weeks, whereas C57BL/6-GKO mice, depending on age, die rapidly or remain chronically infected. The mechanism by which IFN-gamma leads to a protective immunity is yet poorly understood. In order to investigate the effect of IFN-gamma on other cytokines expressed in the intestinal mucosa during C. parvum infection, we studied cytokine mRNA expression in the neonates and GKO (neonatal and adult) mice by quantitative reverse transcription-PCR (RT-PCR) at 4 and 9 days after infection. IFN-gamma mRNA levels were quickly and strongly up-regulated in the mucosa of neonatal mice. In GKO mice, the Th1-type response was dramatically altered during the infection, whereas the mRNA expression levels of the Th2-type cytokines interleukin 4 (IL-4) and IL-10 were increased in both mouse models. In the absence of IFN-gamma, the adult knockout mice up-regulated the mRNA levels of inflammatory cytokines, such as IL-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor, in the mucosa, but not tumor necrosis factor alpha (TNF-alpha), whereas all these cytokines were up-regulated in the infected neonatal mice. Further experiments indicated that injections of TNF-alpha into GKO adult mice significantly reduced oocyst shedding. The results of the present study indicate that the resolution of infection is dependent on the expression of Th1-type cytokines in the mucosa of C57BL/6 mice and that TNF-alpha may participate in the control of parasite development.
Lacroix
S
S
Laboratoire de Protozoologie, Unité de Pathologie Aviaire et de Parasitologie, INRA de Tours, 37380 Nouzilly, France. slacroix@tours.inra.fr
Mancassola
R
R
Naciri
M
M
Laurent
F
F
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D003457:Cryptosporidiosis / Q000188:drug therapy / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D007082:Ileum / Q000033:anatomy & histology / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency*; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*; D015854:Up-Regulation
D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse