Chlamydiae and polymorphonuclear leukocytes: unlikely allies in the spread of chlamydial infection

Abstract

While much is known about the attachment of the chlamydiae to the host cell and intracellular events during the developmental cycle, little is known about the mechanism(s) by which elementary bodies exit the cell. In this report, we use the guinea pig conjunctival model of Chlamydia caviae infection to present in vivo ultrastructural evidence supporting two mechanisms for release of chlamydiae from the mucosal epithelia. Four days after infection, histopathologic observation shows an intense infiltration of polymorphonuclear leukocytes (PMN) in the conjunctival epithelium. By transmission electron microscopy, a gradient-directed PMN response to chlamydiae-infected epithelial cells was observed. As PMN infiltration intensifies, epithelial hemidesmosome/integrin/focal adhesion adherence with the basal lamina is disconnected and PMNs literally lift off and release infected superficial epithelia from the mucosa. Many of these infected cells appear to be healthy with intact microvilli, nuclei, and mitochondria. While lysis of some infected cells occurs with release of chlamydiae into the extracellular surface milieu, the majority of infected cells are pushed off the epithelium. We propose that PMNs play an active role in detaching infected cells from the epithelium and that these infected cells eventually die releasing organisms but, in the process move to new tissue sites via fluid dynamics.

Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

“…Thus, increased gonococcal colonization due to chlamydial infection may lead to increased transmission from a coinfected female to a male partner. In addition, the spread of Chlamydia both to the upper reproductive tract of the infected host and to an uninfected partner may be facilitated by the host PMN response, as proposed by Rank et al from studies with C. caviae in a guinea pig genital tract infection model (64). The increased PMN influx observed in coinfected female mice might then be expected to lead to increased transmission from a coinfected female to a male partner.…”

Effect of Inflammatory Response on In Vivo Competition between Two Chlamydial Variants in the Guinea Pig Model of Inclusion Conjunctivitis

“…It was also of interest in our dose-response experiments that at two doses (10 3 and 10 4 IFU), AZ 2 actually reached higher levels than SP 6 . That PMNs are an active participant in the conjunctival C. caviae infection was visualized by us in a recent transmission electron microscopy study (11). We reported that C. caviae was restricted to infection of the superficial epithelial cells and that PMNs were the only inflammatory cell in contact with chlamydia-infected cells.…”

Identifying a Role for Toll-Like Receptor 3 in the Innate Immune Response to Chlamydia muridarum Infection in Murine Oviduct Epithelial Cells

“…It is widely accepted that the neutrophil is viewed as a professional phagocyte whose sole function in immunity is to engulf, kill, and clear bacteria in response to infection. However, neutrophils have been implicated in host tissue damage in Chlamydial infections, including guinea pig ocular chlamydial infection models (51). Recent investigations into the role of neutrophil involvement in Chlamydia pathogenesis revealed that neutrophil depletion dramatically decreased ocular pathology both clinically and histologically and that there was an associated alteration in adaptive immunity (26).…”