Effect of Inflammatory Response on In VivoCompetition between Two Chlamydial Variants in the Guinea Pig Model of Inclusion Conjunctivitis

ABSTRACTIn order to study the interaction of variants in in vivoinfection, we employed an azithromycin-resistant mutant (AZ2) and its wild-type parent (SP6) in the guinea pig model of Chlamydia caviaeconjunctival infection. When each strain was inoculated individually into conjunctiva, both attained the same level of growth, but AZ2elicited less pathology. However, when equal numbers of the two strains were inoculated together into the guinea pig conjunctiva, SP6produced a significantly greater number of inclusion-forming units than AZ2, and the pathology reflected that of a SP6monoinfection. The goal of this study was to further characterize the dynamics of concomitant infection of these two distinct variants, with particular emphasis on the impact of the host response on the in vivogrowth of each organism and the development of pathology. Animals infected with AZ2had reduced conjunctival infiltration with CD45+cells and neutrophils as well as a reduced interleukin-8 (IL-8) response. Gene expression of gamma interferon (IFN-?), tumor necrosis factor alpha (TNF-a), CCL2, and CCL5 was also significantly lower in AZ2-infected animals. The lower inflammatory response induced by AZ2was associated with its decreased ability to activate NF-?B via Toll-like receptor 2 (TLR2). In general, the inflammatory response in animals infected with both variants was greater than in infection with AZ2alone, resulting in lower numbers of AZ2than those of SP6in the mixed infection. Our results suggest that the ability to elicit an inflammatory response is an important factor in the dynamics of mixed infection with strains that display different pathological phenotypes.