Molecular mimicry and horror autotoxicus: do chlamydial infections elicit autoimmunity?

Abstract

All species of the order Chlamydiales are obligate intracellular eubacterial pathogens of their various hosts. Two chlamydial species, Chlamydia trachomatis and Chlamydia pneumoniae, are primarily human pathogens, and each is known to cause important diseases. Some strains of C. trachomatis are sexually transmitted and frequently cause severe reproductive problems, primarily in women. Other strains of the organism serve as the aetiological agents for blinding trachoma, still the leading cause of preventable blindness in underdeveloped nations. C. pneumoniae is a respiratory pathogen known to cause community-acquired pneumonia. Importantly, both organisms engender an immunopathogenic response in the human host, and both have been associated with widely diverse, relatively common and currently idiopathic chronic diseases, most of which include an important autoimmune component. In this article, we explore the available experimental data regarding the possible elicitation of autoimmunity in various contexts by chlamydial infection, and we suggest several avenues for research to explore this potentially important issue further.

Inflammatory- and immune responses in relation to bacterial replication in mice following re-infections with Chlamydophila pneumoniae

“…In our study, all the mice produced cHsp60-reactive IgG after the primary infection, and this was boosted considerably by re-infections. Autoimmune mechanisms may play a role in the pathogenesis of chlamydial diseases [35] and C. pneumoniae-specific and hHsp60-specific antibodies have been shown to be independent risk factors for coronary heart disease [36].…”

New insights into Chlamydia and arthritis. Promise of a cure?

“…They have a unique developmental cycle that takes place within membrane-bound cytoplasmic inclusions in eukaryotic host cells (figure 1). 44 These organisms display two forms, the infectious elementary body (EB) and the non-infectious reticulate body. Extracellular EBs attach to permissive cells and are taken up by endocytosis.…”

“…1 44 Morphologically aberrant but viable, metabolically active persistent Chlamydiae display a panel of characteristic changes in gene expression and host cell-dependent energy uptake that are in contrast with those of acute infection (figure 1). 3 47–50 For example, during persistence, expression of the major outer membrane protein gene ( omp1 ) and several genes required for the cell division process are severely downregulated 3 48.…”

Profile of Anti-Chlamydia Immune Responses in Complicated (Infertile) and Non-complicated (Fertile) Genital Infections

“…Besides, the recent reports that certain cytokine profiles of anti-chlamydial immune effectors, are critical for preventing immunopathology [10,11] may offer appropriate screening methods for antigen immuno-toxicity or potential for inducing protective immunity; accordingly, the induction of an appropriate immune profile that include IFN-γ or an inappropriate cytokine profile, such as the absence of IFN-γ or a predominantly Th2 or T17 response [10][11][12][13], and presence of potentially pathogenic properties in the antigen [14][15][16][17][18] are promising vaccine antigen screening and discovery approaches. In addition, the profile of cytokines and immune effectors of an anti-chlamydial immune response in infections with and without pathologic complications may also provide a useful molecular and immunological biomarker for predicting chlamydial pathologies.…”