Journal Article

Immunobiological Outcomes of Repeated Chlamydial Infection from Two Models of Within-Host Population Dynamics

Osgood, Nathaniel D., Zhang, Qian, Vickers, David M.

2009

Overview

Chlamydia trachomatis is a common human pathogen that mediates disease processes capable of inflicting serious complications on reproduction. Aggressive inflammatory immune responses are thought to not only direct a person's level of immunity but also the potential for immunopathology. With human immunobiology being debated as a cause of prevailing epidemiological trends, we examined some fundamental issues regarding susceptibility to multiple chlamydial infections that could have implications for infection spread. We argue that, compared to less-frequent exposure, frequent exposure to chlamydia may well produce unique immunobiological characteristics that likely to have important clinical and epidemiological implications. As a novel tool for studying chlamydia, we applied principles of modeling within-host pathogen dynamics to enable an understanding of some fundamental characteristics of an individual's immunobiology during multiple chlamydial infections. While the models were able to reproduce shorter-term infection kinetics of primary and secondary infections previously observed in animal models, it was also observed that longer periods between initial and second infection may increase an individual's chlamydial load and lengthen their duration of infectiousness. The cessation of short-term repeated exposure did not allow for the formation of long-lasting immunity. However, frequent re-exposure non-intuitively linked the formation of protective immunity, persistent infection, and the potential for immunopathology. Overall, these results provide interesting insights that should be verified with continued study. Nevertheless, these results appear to raise challenges for current evidence of the development of long-lasting immunity against chlamydia, and suggest the existence of a previously unidentified mechanism for the formation of persistent infection. The obvious next goal is to investigate the qualitative impact of these results on the spread of chlamydia.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Algorithms / Animal models / Animals / Antibodies, Bacterial - metabolism / B cells / Bacteria / CD4-Positive T-Lymphocytes - metabolism / CD4-Positive T-Lymphocytes - microbiology / Cell growth / Chlamydia / Chlamydia infections / Chlamydia Infections - epidemiology / Chlamydia Infections - physiopathology / Chlamydia trachomatis - metabolism / Comparative analysis / Complications / Computational Biology/Systems Biology / Computer science / Disease / Disease Models, Animal / Diseases / Ecology/Population Ecology / Epidemiology / Exposure / Health aspects / Humans / Hypotheses / Immune response / Immune system / Immunity / Immunology / Immunology/Immune Response / Immunology/Immunity to Infections / Infections / Infectious Diseases/Bacterial Infections / Infectious Diseases/Epidemiology and Control of Infectious Diseases / Infectious Diseases/Sexually Transmitted Diseases / Inflammation / Kinetics / Lymphocytes / Mathematical models / Mathematics / Measles / Models, Biological / Models, Theoretical / Pathogens / Persistent infection / Population / Population biology / Population Dynamics / Public Health and Epidemiology/Infectious Diseases / Sex industry / Sexually transmitted diseases / STD / Surveillance / Viral infections