Repeated, low dose Chlamydia infections trigger aberrant immune responses and weakened host resistance against secondary challenge

Abstract

Chlamydia trachomatis infections endanger women’s health, but translational gaps between animal models and human disease states persist. I compared immune responses in mice receiving repeated, low dose infections (5X) with Chlamydia muridarum to those generated by a conventional single, high dose infection (1X). While 5X and 1X infection schedules stimulated comparable CD4+ Th1 responses, the 5X infections concomitantly induced strong anti-inflammatory Th2 and regulatory T cell responses, as well as pro-inflammatory Th17 responses. Neutrophil infiltration, which may be associated with severe tissue damage, was substantially elevated in the 5X group. In accordance with the divergent immune responses observed in two groups of mice, mice with a prior 5X infection displayed significantly reduced bacterial clearance rates compared to those with a previous 1X infection during subsequent reinfections. En masse, I demonstrate that repeated, low dose infections produce immune responses in mice that closely resemble immune profile and outcomes in humans.