Early local cytokine profiles in strains of mice with different outcomes from chlamydial genital tract infection

Abstract

In this study, we expand on the examination of genetically determined differences in host responses that correlate with clearance of Chlamydia trachomatis from the genital tract. We infected C57BL/6, BALB/c, and C3H/HeN mice with the mouse pneumonitis agent of C. trachomatis (MoPn). C57BL/6 mice had the shortest course of infection (22 days) and the lowest incidence of severe hydrosalpinx. BALB/c mice also had a short course of infection (25 days), but all developed hydrosalpinx. C3H/HeN mice had the longest course of infection (38 days), and all developed severe hydrosalpinx. Determination of local cytokine responses by enzyme-linked immunosorbent assay (ELISA) of genital tract secretions revealed that the levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were significantly increased in the C57BL/6 and BALB/c strains compared to those in the C3H/HeN strain whereas the level of IL-6 was not different. The level of the neutrophil chemokine macrophage inflammatory protein 2 (MIP-2) was increased during the first week of infection in all three strains but was significantly higher in the BALB/c strain, the strain with the most rapid influx of neutrophils into the genital tract. Prolonged detection of MIP-2 in C3H/HeN mice was associated with a protracted presence of neutrophils in the genital tract. Early increases in the levels of the proinflammatory cytokines TNF-alpha and IL-1beta are associated with earlier eradication of infection in the C57BL/6 and BALB/c strains than in the C3H/HeN strain. Increased levels of MIP-2 and neutrophils in BALB/c and C3H/HeN mice relative to C57BL/6 mice suggest that these responses may contribute to pathology.

FIG. 1

IL-1β and IL-6 levels (means and standard errors of the mean) in genital tract secretions of C57, BALB/c, and C3H mice over the course of primary infection with C. trachomatis MoPn. Levels of cytokines were determined with ELISA kits specific for murine IL-1β and IL-6. Data represent the combined results of three separate experiments (n = 5 or 6 per strain per experiment). Each sample was run in duplicate.

FIG. 2

Comparison of the relative degrees of neutrophil infiltrates in the uterine horns (A) and oviducts (B) of C57, BALB/c, and C3H mice over the course of primary infection with C. trachomatis MoPn. Bars represent median pathology scores calculated from 10 mice of each strain sacrificed at each time point. ∗, P < 0.05 for C57 versus C3H; @, P < 0.05 for BALB/c versus C57 and P < 0.005 for BALB/c versus C3H; ∗∗, P < 0.05 for C3H versus C57.

FIG. 3

MIP-2 and GM-CSF levels (means and standard errors of the mean) in genital tract secretions of C57, BALB/c, and C3H mice over the course of primary infection with C. trachomatis MoPn. Levels of cytokines were determined with ELISA kits specific for murine MIP-2 and GM-CSF. Data represent the combined results of three separate experiments (n = 5 or 6 per strain per experiment). Each sample was run in duplicate.