The Important Role of Dendritic Cell (DC) in iNKT-Mediated Modulation of NK Cell Function in Chlamydia pneumoniae Lung Infection

Abstract

Chlamydia pneumoniae (Cpn) infection causes multiple acute and chronic human diseases. The role of DCs in host defense against Cpn infection has been well documented. The same is true for invariant natural killer T (iNKT) cells and NK cells, but the interaction among cells is largely unknown. In this study, we investigated the influence and mechanism of iNKT cell on the differentiation and function of NK cell in Cpn lung infection and the role played by DCs in this process. We found that expansion of IFN-γ-producing NK cells quickly happened after the infection, but this response was altered in iNKT knockout (KO) mice. The expression of activation markers and the production of IFN-γ by different NK subsets were significantly lower in KO mice than wild-type (WT) mice. Using in vitro DC-NK coculture and in vivo adoptive transfer approaches, we further examined the role of DCs in iNKT-mediated modulation of NK cell function. We found that NK cells expressed lower levels of activation markers and produced less IFN-γ when they were cocultured with DCs from KO mice than WT mice. More importantly, we found that the adoptive transfer of DCs from the KO mice induced less NK cell activation and IFN-γ production. The results provided evidence on the modulating effect of iNKT cell on NK cell function, particularly the critical role of DCs in this modulation process. The finding suggests the complexity of cellular interactions in Cpn lung infection, which should be considered in designing preventive and therapeutic approaches for diseases and infections.

Evasion of Innate Lymphoid Cell-Regulated Gamma Interferon Responses by Chlamydia muridarum To Achieve Long-Lasting Colonization in Mouse Colon

“…Both the killer ILC1s (conventional NK cells) and the helper ILC1s are considered the major sources of innate IFN-␥ (73,74). Innate IFN-␥ produced during chlamydial infection in the airway or genital tract has been attributed to NK cells (21)(22)(23)(24)(25)(26)(27)(28)(29). However, these previous studies did not attempt to differentiate NK cells from other ILCs.…”

“…Besides extracellular and facultative intracellular bacteria (6), the obligate intracellular parasite Toxoplasma gondii has also been shown to interact with ILCs (19,20), although the mechanisms of the T. gondii-ILC interactions remain largely unknown. Knowledge on the interactions of the obligate intracellular bacterium Chlamydia with ILCs is limited, although natural killer (NK) cells have been shown to play important roles in chlamydial infection (21)(22)(23)(24)(25)(26)(27)(28)(29). These previous studies did not differentiate NK cells from non-NK ILCs.…”

Cross Talk Between Natural Killer T and Dendritic Cells and Its Impact on T Cell Responses in Infections

“…Besides its direct effect on DCs, NKT cells can also influence DC function through other types of innate immune cells, such as NK cells. We reported a decade ago that NKT cells, following chlamydial infection, can influence the function of NK cells and NK subsets (46). In addition, we found then that NK cells could influence DC function for the induction of Th1 cells in chlamydial infection (66).…”

“…Notably, the study on the adjuvant effect of NKT or NKT activating lipid antigens to promote DC function represents a significant effort to improve vaccine efficacy Over the past decade, we did a series of studies on NKT cell responses in respiratory tract Chlamydia muridarum and Chlamydia pneumoniae infections, particularly on the feedback of NKT cells on DC function (29,(44)(45)(46)(47)(48). NKT cell responses in human chlamydial diseases have also been reported (49).…”

Innate Lymphoid Cells Are Required for Endometrial Resistance toChlamydia trachomatisInfection

“…For example, information on whether and how ILCs may contribute to endometrial immunity against chlamydial infection may be useful for developing strategies to enhance endometrial resistance to infection and to attenuate endometrial inflammatory pathologies. Although previous studies showed that conventional natural killer (cNK) cells play important roles in chlamydial infection (10)(11)(12)(13)(14)(15)(16)(17)(18), those studies did not differentiate cNK cells from non-NK ILCs. We recently showed that a mutant strain of Chlamydia muridarum was inhibited by ILCs in the mouse colon (19), suggesting that chlamydial intracellular infection can be regulated by ILCs.…”