NK T Cell Activation Promotes Chlamydia trachomatis Infection In Vivo

Abstract

We used two approaches to examine the role of NK T cells (NKT) in an intracellular bacterial (Chlamydia trachomatis mouse pneumonitis (C. muridarum)) infection. One is to use CD1 gene knockout (KO) mice, which lack NKT, and the other is to activate NKT using α-galactosylceramide (α-GalCer), a natural ligand of these cells. The data showed a promoting effect of NKT activation on Chlamydia lung infection. Specifically, CD1 KO mice exhibited significantly lower levels of body weight loss, less severe pathological change and lower chlamydial in vivo growth than wild-type mice. Immunological analysis showed that CD1 KO mice exhibited significantly lower C. muridarum-specific IL-4 and serum IgE Ab responses as well as more pronounced delayed-type hypersensitivity response compared with wild-type controls. In line with the finding in KO mice, the in vivo stimulation of NKT using α-GalCer enhanced chlamydial growth in vivo, which were correlated with reduced delayed-type hypersensitivity response and increased C. muridarum-driven IL-4/IgE production. Moreover, neutralization of IL-4 activity in the α-GalCer-treated BALB/c mice significantly reduced the promoting effect of α-GalCer treatment on chlamydial growth in vivo. These data provide in vivo evidence for the involvement of NKT in a bacterial pathogenesis and its role in promoting Th2 responses during infection.

IL-17/Th17 Promotes Type 1 T Cell Immunity against Pulmonary Intracellular Bacterial Infection through Modulating Dendritic Cell Function

“…1C). It has been reported that ␥␦ T and NKT cells can also produce IL-17 (4,5), and we have shown that both types of these cells are activated by Cm infection (45)(46)(47). Therefore, it is worthwhile to test whether these cells also produce IL-17 and what cell(s) is the major source of the IL-17 produced during chlamydial infection.…”

The glycolipid exoantigen derived from Chlamydia muridarum activates invariant natural killer T cells

“…In our previous study, we showed that iNKT plays an important role in immune responses to chlamydial infections. 30,31 Interestingly, our previous studies have shown that iNKT cells are activated in vivo and produce IFN-c and IL-4. C. pneumoniae infection in mice showed enhanced Th1 cytokine, IFN-c, production by iNKT cells, whereas C. muridarum increased Th2 response reflected by enhanced IL-4 and IL-5 production.…”

“…C. pneumoniae infection in mice showed enhanced Th1 cytokine, IFN-c, production by iNKT cells, whereas C. muridarum increased Th2 response reflected by enhanced IL-4 and IL-5 production. 30,31 In this study, we further explored the molecular nature of chlamydial antigen which activates iNKT cells. Our data from the study showed that GLXA, a previously reported chlamydial glycolipid, can stimulate iNKT hybridoma cell in either cell-free antigen-presentation assay or a DC based assay.…”

“…Further, we have previously reported that iNKT cells are activated in vivo and play an important role in immune responses to chlamydial infections. 30,31 Taking account of these facts, we hypothesized that GLXA might specifically activate iNKT cells. To test the hypothesis, we investigated the role of GLXA derived from Chlamydia muridarum, a mouse biovar of C. trachomatis (also known as mouse pneumonitis) in iNKT cell activation using in vitro as well as in vivo settings.…”

CD1d Ligands: The Good, the Bad, and the Ugly

“…It was found that the C-glycoside induced more of a Th1 (i.e., IFN-␥) response, was longer lasting, and was actually a better adjuvant than the parental compound itself in murine models of malaria and metastatic melanoma (53)(54)(55)(56)(57). Furthermore, ␣-GalCer administration has been shown to be mostly protective activity against viruses (58 -61), bacteria (62)(63)(64)(65)(66)(67), and other pathogens (68,69). In Trypanosoma cruzi, although GPIs and other lipids from this genus can bind to CD1d, those ligands do not stimulate NKT cells (70).…”