Distinct NKT Cell Subsets Are Induced by Different Chlamydia Species Leading to Differential Adaptive Immunity and Host Resistance to the Infections

Abstract

We investigated the role of NKT cells in immunity to Chlamydia pneumoniae and Chlamydia muridarum infections using a combination of knockout mice and specific cellular activation approaches. The NKT-deficient mice showed exacerbated susceptibility to C. pneumoniae infection, but more resistance to C. muridarum infection. Activation of NKT reduced C. pneumoniae in vivo growth, but enhanced C. muridarum infection. Cellular analysis of invariant NKT cells revealed distinct cytokine patterns following C. pneumoniae and C. muridarum infections, i.e., predominant IFN-γ in the former, while predominant IL-4 in the latter. The cytokine patterns of CD4+ and CD8+ T cells matched those of NKT cells. Our data provide in vivo evidence for a functionally diverse role of NKT cells in immune response to two intracellular bacterial pathogens. These results suggest that distinct NKT subsets are induced by even biologically closely related pathogens, thus leading to differential adaptive immune response and infection outcomes.

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.…”

Immune-mediated control of Chlamydia infection

“…The factors that determine whether a Th1 or a Th2 response develops following Chlamydia infection is largely unknown, but will be important to understand in order to develop a vaccine that will stimulate protective and not pathological outcomes. Recent experiments comparing immune responses against different species of Chlamydia have suggested that NKT cells may be an important determinant of the Th1/Th2 bias during Chlamydia infections (Joyee et al, 2007).…”

Enhanced Inducible Costimulator Ligand (ICOS-L) Expression on Dendritic Cells in Interleukin-10 Deficiency and Its Impact on T-Cell Subsets in Respiratory Tract Infection

“…The isolated CD4 + T cells were cocultured with purified DCs in the presence of ultraviolet-inactivated Cm as described (54). In designated experiments, anti-ICOS-L mAbs (10 μg/mL, clone HK5.3; eBioscience) were added to the coculture wells to block ICOS-L signal pathway (51).…”

“…Spleen and lungs were aseptically removed. To analyze cytokine production, single-cell suspensions were prepared from spleen and lungs as described previously (53,54). The cells were cultured at a concentration of 7.5 × 10 6 cells/mL (splenocytes) or 5.0 × 10 6 cells/mL (lung cells), respectively, in complete culture medium with or without stimulation of ultraviolet-inactivated Cm (10 5 IFU/mL).…”

“…Cm-specific CD4 + T cells were isolated from the spleen of Cm-immunized mice by using a CD4 magnetic cell sorting buffer (MACS)-positive selection column (Miltenyi Biotec, Auburn, CA, USA) as described (54). DCs were isolated from spleen of WT or IL-10 KO mice by using magnetic CD11c columns from MACS.…”