title: Th1 cytokine responses fail to effectively control Chlamydia lung infection in ICOS ligand knockout mice.
abstract: ICOS ligand (ICOSL) plays an important role in controlling specific aspects of T cell activation, differentiation, and function. Th1-type immune responses have been shown to be critical in host defense against chlamydial infections. To assess the role of ICOSL-ICOS interaction in host defense against chlamydial infection, we compared the immune responses and pathological reactions in ICOSL gene knockout (KO) and wild-type (WT) mice following Chlamydia muridarum lung infection. The results showed that ICOSL KO mice exhibited greater body weight loss, higher pathogen burden, and more severe histopathology in their lung than did WT mice. Cytokine analysis revealed that ICOSL KO mice produced lower levels of Th2 (IL-4 and IL-5) and anti-inflammatory (TGF-beta1 and IL-10) cytokines, but higher Th1-related (IFN-gamma and IL-12p40/IL-23) and proinflammatory (IL-6 and TNF-alpha) cytokines. ICOSL KO mice also showed reduced Chlamydia-specific Ab levels in their sera and lung homogenates. In addition, ICOSL KO mice demonstrated significantly lower ICOS expression in T cells and lower Th17 responses than did WT mice. Finally, we showed that ICOS-ICOSL interaction and cell-cell contact are essential for CD4(+) T cells to inhibit chlamydial growth in the cultured lung fibroblasts. The data suggest that ICOSL plays a significant role in immunoregulation and protective immunity against Chlamydia infections and that the Th1 skew in cytokine responses per se is not sufficient for effective control of Chlamydia infections.
authors.affiliation: Laboratory for Infection and Immunity, Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Kamran
authors.initials: K
authors.lastname: Kadkhoda
authors.forename: Shuhe
authors.initials: S
authors.lastname: Wang
authors.forename: Antony George
authors.initials: AG
authors.lastname: Joyee
authors.forename: Yijun
authors.initials: Y
authors.lastname: Fan
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002469:Cell Separation; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011506:Proteins / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D011506:Proteins