Murine Models of Chlamydia trachomatis Genital Tract Infection: Use of Mouse Pneumonitis Strain versus Human Strains

Morrison and Morrison (11) analyzed by in situ immunohistochemistry the progression of the inflammatory and cytokine responses in the genital tracts of mice. They provided an important foundation from which we can study the effects of experimentally induced perturbations in the systemic immune response on the development of local genital tract immunity. The observed cytokine responses were obtained using the Chlamydia trachomatis strain mouse pneumonitis (MoPn).

The MoPn agent, the mouse biovar of C. trachomatis, is much more virulent in mice than human strains (14), causing acute pathology throughout the genital tract and characteristically resulting in systemic infection (12). In addition, the developmental cycle of MoPn is more rapid, its duration being approximately half that of human strains, and the strain is more prolific. However, in humans the urogenital C. trachomatis serovars cause no systemic infections and upper genital tract progression, followed by pathology, usually resulting from multiple infections, is only seen in a small percentage of women (3, 13).

We have shown an important role for gamma interferon (IFN-γ) in the early clearance of chlamydia from the genital tract (4). When we infected IFN-γ^−/− mice with MoPn we observed no significant differences in the clearance of chlamydiae between infected and control mice. However, when we infected animals with the human genital isolate (5, 6, 9) serovar D, we saw striking differences in infection kinetics between IFN-γ^−/− and control animals beginning as early as day 4 and continuing throughout the observation period (70 days). Thus, the MoPn strain and the human C. trachomatis strains differ in response to at least one important cytokine and most likely will be found to differ in response to other cytokines.

Recently, a novel high-resolution technique has been introduced for whole-genome analysis: amplified fragment-length polymorphism (AFLP). This technique has proven its usefulness as a tool in bacterial taxonomy and epidemiology. It was shown that human isolates were clearly different from the MoPn strain of C. trachomatis (10). Both the AFLP and DNA-DNA hybridization demonstrate that the MoPn strain should be considered a separate Chlamydia species. Indeed, Everett et al. (2) proposed a reclassification of the order Chlamydiales and its current taxa based on phylogenetic analyses of the 16S and 23S rRNA genes with corroborating genetic and phenotypic information. This interesting proposal was the first topic on the program of the 4th European Chlamydia Congress in August this year (Helsinki, Finland). One of the proposed new species in this reclassification is Chlamydia muridarum sp. nov. Thus, it is the considered opinion of bacterial taxonomists that the MoPn strain differs considerably from human C. trachomatis strains.

Finally, although both in animal models and in humans specific major histocompatibility complex class I alleles and HLA types were found to be independently associated with pelvic inflammatory disease and tubal infertility (1, 7, 8), repeated pelvic inflammatory disease periods and repeated C. trachomatis infections increase the risk for tubal infertility significantly (3, 13). This is most likely based on enhanced autoimmune reactivities, including heat shock protein 60 autoimmunity. This demonstrates that proteins expressed by the microorganism are the determinants for the immunologic response of the host, emphasizing the importance of the choice of the chlamydial strain to be used as a model for genital tract infection.

Thus, it seems to be worthwhile and potentially clinically more relevant to investigate the cytokine profiles in the murine genital tract during the course of infection using human C. trachomatis strains and to compare those cytokine responses to the results obtained with the MoPn agent. Through this comparison, a basis for the selection of the most appropriate strain for use in murine models of human genital tract infection can be made.