An in vitro Model of Chlamydia trachomatis Infection in the Regenerative Phase of the Human Endometrial Cycle

Abstract

An in vitro model of the regenerative phase of the human endometrial cycle was developed in order to study the growth of Chlamydia trachomatis during the period following menses. Glandular epithelial fragments were prepared from curettings of endometria and explanted onto coated substrata. Epithelial cells migrated rapidly from the explant in a fashion which closely mimicked the regeneration of the surface epithelium after menses. The cultures were then experimentally infected with C. trachomatis serotype E at various times during formation of the outgrowth. Chlamydia1 inclusions developed both within the explants and in the outgrowing epithelial sheets. They were also found in isolated epithelial and non-epithelial cells. However, the most striking feature of chlamydial inclusion development within these cultures was the tendency for inclusions to be located in cells at the periphery of the epithelial sheets. This was partly due to the failure of the cells within the sheets to bind chlamydiae after centrifugation of the organisms onto the culture and partly due to a phenomenon similar to phagokinesis. During this process infectious chlamydial particles were cleared from the substratum by migrating cells with free motile edges, which occasionally led to internalization and inclusion development within these cells.

The Development of Chlamydia trachomatis Inclusions within the Host Eukaryotic Cell during Interphase and Mitosis

“…Local retention of EBs on the extracellular matrix (Campbell et al, 1988) or in the mucus bathing the apical surface of cells could produce a locally high concentration of EBs and thus lead to multiple infection and rapid growth of inclusions due to inclusion fusion. Paradoxically this would not be the most effective means of amplification of the infection.…”

“…McCoy cells were cultured in the same medium except that no growth factor or hormones were used to supplement the medium. The cells or glandular fragments were plated into collagen-coated (Campbell et al, 1988) glass-bottomed flasks (Allen, 1987) and infected immediately before recording was started. All observations on living cells were made before 96 h of culture.…”

Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis.

“…In addition, women exposed to partners with gonorrhea are more likely to yield chlamydiae if they become infected with N. gonorrhoeae than if they do not (83). In addition to gonococcal infection, trauma to the genital tract is thought to stimulate mucosal turnover, potentially triggering the conversion of persistent chlamydiae to an active growth phase (19). With the constant fluctuation in environmental conditions, a number of undefined factors (immune factors, nutrients, and hormones in genital infections) may stimulate a productive infection.…”

The immunobiology and immunopathology of chlamydial infections

“…In general, chlamydia] activity is greatest in host cells which are themselves actively growing and dividing. Thus, if mucosal cell turnover is increased by trauma or coincident infection, quiescent chlamydial infection might be activated (25,139). Support for this hypothesis came from observations that the isolation of C. trachomatis from the genital tracts of female contacts of men with gonococcal urethritis was dependent not only on the presence of chlamydiae in the male partner, but also on actual infection by N. gonorrhoeae in the woman herself (6, 78,119).…”