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Introduction Chlamydia trachomatis (Ct) infections severely impact women’s health due to pelvic inflammatory disease (PID), and, for unclear reasons, repeated infections are correlated with severity. Contributions from animal studies, using a single inoculation, have imparted valuable findings, but utilizing a repeated infection model could expand the understanding of Ct driven tissue damage. We hypothesize that, compared to single infections, repeated Chlamydia infection dysregulates the immune response, and results in more severe pathology. Methods We inoculated mice with C. muridarum (Cm) using the conventional, single dose (1 dose of 6*10^5 IFU; 1X), or repeated, low dose infections with the same cumulative number of bacteria (5 doses of 1.2*10^5 IFU; 5X), and assessed the cellular, molecular, and pathology indicators of their immune response on days 10, 23, and 30 post-initial infection. Results Following 5X infection, pathology severity, indicated by oviduct cyst diameter, was significantly increased compared to the 1X group. This increase was associated with significantly elevated neutrophilic influx and pro-inflammatory cyto/chemokine concentrations in the genital tracts of 5X, but not 1X, infected animals, denoting differential host responses. IgG1 levels were markedly higher in the 5X group, while IgG2a levels were significantly higher in the 1X group, suggesting a skewed Th2 response in the 5X group, indicating a potential mechanism of pathology development following repeated infections. Variances in bacterial burden did not account for these differences, as both groups had similar levels of bacterial shedding. Conclusions Repeated Cm exposure induces a distinct molecular response, triggering maladaptive neutrophil recruitment, leading to a pathogenic modulation of T helper responses that promote tissue damage. These findings demonstrate the potential of repeated infection models to provide insight into the immune and pathology states in humans, and may be of value in elucidating, and targeting interventions to, host mediators of tissue damage during Ct infection. |
