ABSTRACT
LIGHT, a costimulatory member of the immunoglobulin superfamily (Ig SF), can greatly impact T cell activation. The role of the LIGHT signaling pathway in chlamydial infection was evaluated in mice following respiratory tract infection with Chlamydia psittaci. Compared with wild type (WT) mice, LIGHT knockout (KO) mice showed significant reduction of body weight, much lower survival rate, higher bacterial burden, prolonged infection time courses and more severe pathological changes in lung tissue. The mRNA levels of IFN-γ, TNF-α, IL-17 and IL-12 in the lung tissue of LIGHT KO mice were significantly lower than those in WT mice. While there was no obvious difference in the percentages of CD4+ and CD8+ T cells in the spleens of the two groups of mice, there was a markedly elevated percentage of CD4+ CD25+ FoxP3+ Treg cells in LIGHT KO mice. Together, these results demonstrate that the LIGHT signaling pathway is not only required for inflammatory cytokine production as part of the host response to chlamydial infection, but also influences the differentiation of CD4+ CD25+ FoxP3+ Treg cells, both of which may be essential for control of C. psittaci respiratory tract infection.
Subject(s)
Chlamydophila psittaci/immunology , Chlamydophila psittaci/pathogenicity , Psittacosis/pathology , Signal Transduction , Tumor Necrosis Factor Ligand Superfamily Member 14/deficiency , Animals , Bacterial Load , Body Weight , Cytokines/analysis , Cytokines/genetics , Disease Models, Animal , Gene Expression Profiling , Mice , Mice, Knockout , Psittacosis/microbiology , RNA, Messenger/analysis , RNA, Messenger/genetics , Severity of Illness Index , Survival Analysis , T-Lymphocyte Subsets/immunologyABSTRACT
OBJECTIVE: To study the role of lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT) in the development of protective immunity and pathology during Chlamydia Muridarum urogenital infection in mice. METHODS: C57BL/6J wild type (wt) and mice deficient in LIGHT (LIGHT KO) were inoculated intravaginally with 1 x 10(4) IFUs of live C. muridarum organisms. Half mice of each group were reinfected on day 49 after primary infection. We took mice vaginal swabs every 3 or 4 days to monitor live organism shedding. On day 80 after the primary infection, mice were sacrificed, the vaginal tract was isolated for pathology analysis. The spleen cells were collected and IL-4, IL-5, IL-17 and IFN-y were detected by ELISA in the spleen cells culture supernatant after restimulated by UV-MoPn EB. The titers of different Ab isotypes were measured in mice serum by Indirect Immunofluorescence Assay. RESULTS: The chlamydia shedding time of LIGHT KO mice was similar to wild type mice, which cleared the organisms within 28 days after primary infection, and acquired protective immunity against C. muridarum reinfection. All mice regardless of genotypes developed severe upper genital tract pathology and showed no significant difference between LIGHT KO and wild type mice. All mice developed robust anti-C. muridarum organism IgG antibody responses and the ratios of IgG2a versus IgG1 showed no significant difference between LIGHT KO and wild type mice. Splenocytes from MoPn-infected LIGHT KO and wild type mice produced high levels of IFN-gamma and IL-17, but IL-4 and IL-5 couldn't be detected. CONCLUSIONS: LIGHT signal pathway may not correlated with protection against C. muridarum urogenital tract infection and urogenital tract pathology induced by C. muridarum.
