Role of NK Cells in Early Host Response to Chlamydial Genital Infection

Abstract

The cell-mediated immune response has been documented to be the major protective immune mechanism in mice infected genitally with the agent of mouse pneumonitis (MoPn), a biovar of Chlamydia trachomatis. Moreover, there is strong evidence to indicate that gamma interferon (IFN-γ) is a major effector mechanism of the cell-mediated immune response. Previous studies from this laboratory have also reported that the dominant cell population in the genital tract is the CD4 Th1 population. When experiments were performed by the enzyme-linked immunospot assay, high numbers of cells producing IFN-γ were found in the genital tract, concomitant with resolution of the infection; however, in addition, an increase in IFN-γ-producing cells which were CD4− was seen early in the infection. Since natural killer (NK) cells produce IFN-γ and have been found to participate in the early responses in other infections, we hypothesized that NK cells are responsible for early IFN-γ production in the murine chlamydial model. NK cells were quantified by the standard YAC-1 cytotoxicity assay and were found to appear in the genital tract as early as 12 h after intravaginal infection with MoPn. The cells were confirmed to be NK cells by abrogation of YAC-1 cell cytotoxicity by treatment in vitro and in vivo with anti-asialo-GM1. The early IFN-γ response could also be depleted by treatment with anti-asialo-GM1, indicating that NK cells were responsible for the production of this cytokine. Of interest was our observation that depletion of NK cells also exacerbated the course of infection in the mice and elicited a Th2 response, as indicated by a marked increase in immunoglobulin G1 antibody. Thus, these data demonstrate that NK cells are not only responsible for the production of IFN-γ early in the course of chlamydial genital tract infection but are also, via IFN-γ, a significant factor in the development of the Th1 CD4 response and in the control of the infection.

Infection of epithelial and dendritic cells byChlamydia trachomatisresults in IL-18 and IL-12 production, leading to interferon-γ production by human natural killer cells

“…IFN-c is central to the immune response to C. trachomatis. C. trachomatis-infected women have higher levels of IFN-c in endocervical secretions than uninfected women [15] and this has also been demonstrated in vivo in murine infection by Chlamydia muridarum [7,16]. Studies using antibody depletion of IFN-c, IFN-c gene knockout mice, or IFN-c receptor gene knockout mice have all shown that IFN-c has a significant role to play in immune defence against various species of chlamydiae [5,6,[17][18][19][20][21].…”

TLR3 Deficiency Leads to Altered Immune Responses toChlamydia trachomatisInfection in Human Oviduct Epithelial Cells

“…Conversely, TLR3 deficiency in hOE cells resulted in the increased synthesis of CCL5 and the type III interferon IL-29 (IFNλ1) throughout infection, and IL-28A (IFNλ2) late in infection (Figures 6 and 7). Collectively, these data demonstrate a putative role for TLR3 in the acute phase of the innate immune response to Chlamydia that is known to occur early during infection in vivo ( 17, 39–42 ), and that TLR3 has some role in modulating mediators of the adaptive immune response (43).…”

Fc receptor regulation of protective immunity against Chlamydia trachomatis

“…Besides, a potential role for NK cells in anti-chlamydial immunity during reinfection is suggested by their expression of CD16 or the FccRIII, which binds IgG for ADCC, and NK cells have been associated with Th1 development and early clearance of chlamydia in mice. 45 As the FcR de®ciency evaluated in this study [i.e. FccRI (CD64) and FcRcIII (CD16)] excludes the receptor for IgA (CD89), the role of the latter in mediating protection during a secondary infection is unclear.…”