Protection against Ascending Infection of the Genital Tract byChlamydia trachomatisIs Associated with Recruitment of Major Histocompatibility Complex Class II Antigen-Presenting Cells into Uterine Tissue

Abstract

A mouse model of ascending infection following intravaginal inoculation with a strain of Chlamydia trachomatis isolated from humans has been used to identify immune mechanisms associated with protection against genital infection. BALB/c and C3H mice differed in their susceptibilities to infection and inflammatory disease. In both mouse strains, ascension of the organism and recruitment of bone marrow-derived mononuclear leukocytes were evident in uterine tissue 1 week postinfection. By 3 weeks the organism had been cleared and inflammation had been resolved in the BALB/c mice, but both persisted in the C3H animals. In athymic nude BALB/c mice both the organism and inflammation persisted, indicating the influence of the hosts' immune response on the outcome of infection. Both BALB/c and C3H mice had a Th1 response in draining lymph nodes, with predominant production of gamma interferon and tumor necrosis factor alpha, low levels of interleukin-10, and no detectable levels of interleukin-4. However, the composition of the early uterine infiltrate differed in these two mouse strains. Cell surface labeling and analysis of light scatter properties by flow cytometry identified a population of large, CD45 ؉ major histocompatibility complex class II mononuclear cells, which were a prominent feature of the infiltrates in BALB/c mice but were present in significantly lower numbers in C3H mice. These cells expressed the costimulatory molecules CD86 and CD40 and stimulated allogeneic T cells, suggesting that these mononuclear cells are a population of antigen-presenting cells and that they may play a role in clearing antigen and protecting against inflammatory disease in BALB/c mice. An additional level of immunological control may thus exist in genital chlamydial infection.

Mucosal delivery of CpG oligodeoxynucleotides expands functional dendritic cells and macrophages in the vagina

“…2,3 In the genital tissue, protection against Chlamydia trachomatis is associated with recruitment of MHC class II-positive cells to the uterine tissue. 44 IVAG CpG-ODN has been shown by our lab and others to induce protection from IVAG HSV-2 challenge only when given within 2 days before HSV-2 challenge. 20,42 Specifically, we have shown that IVAG CpG-ODN delivery 1 day prior to HSV-2 challenge is protective, while challenge at 3 days post CpG-ODN is not.…”

Effects of inoculating dose on the kinetics of Chlamydia muridarum genital infection in female mice

“…The chlamydial burden seen in the uterine horns was much lower than that observed in the oviducts. Recruitment of CD45 + major histocompatibility complex class II (MHC II) cells limit the level of infection in uterine tissues early in infection, 24 suggesting that an early MHC II response may have limited the level of infection within the uterine tissues in this case. The cervico-vaginal regions had a greater overall chlamydial burden than that of the uterine and oviduct tissues and a more prolonged infection.…”

Induction of protective immunity against a Chlamydia trachomatis genital infection in three genetically distinct strains of mice

“…17±19, 21 Furthermore, signi®cant differences in the innate and acquired immune responses have been reported between these three strains of mice following a genital and a pulmonary infection. 17,18,21,22 We have previously shown that intranasal immunization of BALB/c mice with elementary bodies (EB) of C. trachomatis mouse pneumonitis (MoPn) results in an immune response that can protect the animals against a genital challenge. 23,24 Thus, here we wanted to determine if it was possible to induce a protective immune response against a C. trachomatis genital challenge in three genetically unique strains of mice that have marked differences in susceptibility and immune response to a chlamydial infection.…”