Protection against ascending infection of the genital tract by Chlamydia trachomatis is associated with recruitment of major histocompatibility complex class II antigen-presenting cells into uterine tissue.
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.
Antigen Presentation Research Group, Imperial College School of Medicine at Northwick Park Institute for Medical Research, Harrow, Middlesex HA1 3UJ, United Kingdom. a.stagg@ic.ac.uk
A J
AJ
Stagg
M
M
Tuffrey
C
C
Woods
E
E
Wunderink
S C
SC
Knight
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D002692:Chlamydia trachomatis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014599:Uterus / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen; D017493:Leukocyte Common Antigens