Persistent Chlamydial Infections: An In Vivo Reality or a Cell Culture Artifact?

KEY WORDS .t racomatis;. pneumoniae; chronic upper genital tract infection aa/amydia tracaomatis and CMamydia pneumoniae re pathogens with an extremely narrow host range (humans) and are limited to existence within the confines of a membrane-bound vesicle contained in the cytoplasm of susceptible host cells. In the case of C. tracomatis, with the notable exception of the lymphogranuloma venereum biovar, active growth and progression to a productive infection, with generation of infectious forms (elementary bodies, EB), appears to be restricted to epithelial cells lining either ocular (conjunctiva) or genital (urethra in males, endocervix to fallopian tubes in females) mucosal surfaces, although spread to deeper tissue and in the case in Reiter's disease, synovium, is possible. In the case of (7. pneumoniae, a broader host cell range exists that includes respiratory epithelial cells, alveolar macrophages and perhaps monocytes and cells of the vascular endo-thelium. Long term sequelae ofacute human 6". trachomatis and 6".pneumoniaeinfections include chronic local tissue damage that may reflect persistent or occult infection , alone or superimposed upon reinfection that lead to immunologic consequences which are directly associated with disease manifestations. Chronic aspects of chlamydial infections include scarring trachoma, damage to fallopian tubes for 6". tracomatis and possibly development of atheroscle-rotic lesions for C.pneumoniae. At present it is unclear what, if any, role persistent, viable but metabolically quiescent chlamydiae play in the more chronic aspects of human chlamydial infections, but extensive cell culture studies have provided evidence that chlamydial persistence in the form of aberrently Article growing organisms can be induced by a variety of external stimuli and more recently in vivo data has in large measure supported claims made based on cell culture models of persistence. Chlamydia normally proceed through an orderly alternation of functionally and morphologically distinct developmental forms that begin and end with the production of metabolically inactive, infectious EB, interspersed with the metabolically active, but non-infectious intracellular form called the reticu-late body (RB). Productive infections necessarily begin and end with EB, but a variety of cell culture manipulations can be introduced that prevent or delay RB from differentiating to EB. The result of these manipulations extend the length of time non-infectious RB remain within intracellular cyto-plasmic vesicles and often this extended period of non-productive growth is associated with the development of morphologically abnormal (often very large) intracellular forms of the organism. Variations of these alternative growth options have been studied in the context of antibiotic treatments …