This pathogen matures and reproduces in the intestine The juveni

This pathogen matures and reproduces in the intestine. The juvenile

form, or newborn larva, enters the mesenteric vasculature and is carried to the liver by the portal vein. Beyond the liver, newborn larvae circulate systemically and may penetrate skeletal muscle cells, where they grow and await ingestion of the host to renew the life cycle. In our current studies, we have begun to investigate the mechanisms underlying hepatocyte injury and death. Our results demonstrated that the progression of initial hepatocyte damage into organized regions CHIR-99021 datasheet of necrosis was controlled by the prevailing cytokine environment. Although the absence of IL-10 led to cellular injury during infection, IL-4 was required for the evolution to necrotizing hepatitis. These results support a critical role for IL-4 in controlling the progression of hepatic inflammation after enteric parasitic infection, and they illustrate the importance of the enterohepatic cytokine balance for appropriate hepatic immune function.

ALT, alanine aminotransferase; CCR9, chemokine (C-C motif) receptor 9; GALT, gut-associated lymphoid tissue; IgG, immunoglobulin G; IL, interleukin; RO4929097 KO, knockout; Ly6-G, lymphocyte antigen 6 complex locus G; NK, natural killer; PBS, phosphate-buffered saline; WT, wild type. C57BL/6 and IL-10 KO (on a C57BL/6 background) mice were purchased from the Jackson Laboratory (Bar Harbor, ME). IL-4 KO and IL-10/IL-4 KO mice were a generous 上海皓元 gift from Dr. Tom Wynn at the National Institutes of Health. PHIL (eosinophil deficient) mice were provided by Dr. Jamie Lee at the Mayo Clinic. These mice were bred onto an IL-10 KO background, and transgenic mice were identified as described. 10 Disruption of the IL-10 locus was confirmed by polymerase

chain reaction with primer sequences previously listed. 8 Animals were bred and housed at Cornell University, a facility accredited by the American Association for Accreditation of Laboratory Animal Care. Studies were approved by the Institutional Animal Care and Use Committee. T. spiralis first-stage larvae were recovered from the muscles of irradiated Albino Oxford rats by digestion with 1% pepsin in acidified water as described previously. 11 Experimental mice were administered 600 first-stage larvae by gavage. In some experiments, mice were given a control rat immunoglobulin G (IgG) or were rendered neutropenic by the injection of an α-granulocyte receptor-1 (Gr-1) antibody (clone RB6-8C5), as described previously, 12 or clone NIMP-R14, a kind gift from Dr. Fabienne Tacchini-Cottier. 13 RB6.8C5 recognizes Gr-1, which is expressed by other cell types in addition to neutrophils, albeit at lower levels. 14 NIMP-R14 recognizes a 25- to 30-kDa protein present on the neutrophil surface and is reported to be specific.

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