Complement activation and stimulation of chemotaxis by Chlamydia trachomatis

Abstract

The stimulus for the migration of polymorphonuclear leukocytes (PMNs) in acute chlamydial infection was studied in vitro by examining the chemotaxigenic effect of L2 and DE Chlamydia trachomatis elementary bodies (EB) upon the plasma of three healthy donors. In each individual experiment, chemotactic response was assessed with PMNs and plasma from the same respective donor, and no specific antibodies against C. trachomatis were detected in the plasma of any donor. Chemotaxis was observed in an agarose plate assay and was quantitated as the chemotactic differential, or CD (directed migration of PMNs minus random movement of PMNs). For each donor, the mean CD was significantly greater (P less than 0.005) when plasma preincubated for 2 h with L2 EB was used as the chemoattractant than when (i) plasma alone, (ii) plasma preheated to 56 degrees C for 30 min before incubation with L2 EB, or (iii) L2 EB in phosphate-buffered saline (PBS) was used as the potential chemoattractant. Similarly, in the one donor in whom DE EB were studied, the mean CD was also significantly greater (P less than 0.005) for plasma preincubated with DE EB as compared with (i) plasma alone or (ii) DE EB in PBS. Complement activation by C. trachomatis EB was assessed by radioimmunoassay for C5a des-arginine in all chemoattractant preparations used in the chemotaxis assay. Mean C5a des-arginine levels were high in plasma samples preincubated with L2 EB (171.00 +/- 10.64, 107.00 +/- 4.76, and 89.70 +/- 1.74 ng per ml) or DE EB (37.40 +/- 15.76 ng per ml) but were undetectable (less than 4.0 ng per ml) in (i) plasma alone, (ii) preheated plasma incubated with L2 EB, and (iii) PBS containing L2 EB. Thus, L2 EB and DE EB of C. trachomatis exert a chemotaxigenic effect upon normal antibody-negative plasma, and this effect is at least in part a result of complement activation and generation of the potent chemotaxin C5a.

Tumor necrosis factor alpha activity in genital tract secretions of guinea pigs infected with chlamydiae

“…Thus, the primary stimulus for the initiation of the acute inflammatory response should be the organism itself. Chlamydial EBs bind C3 and thereby initiate the alternative complement pathway (14); the binding site was found to be the chlamydial major outer membrane protein. However, a role for chlamydial lipopolysaccharide (LPS) in the initiation of the alternative pathway cannot be ruled out, especially since LPS is expressed in large amounts on the surfaces of infected cells early in the infection cycle (10,22).…”

Localization of Chlamydia trachomatis Heat Shock Proteins 60 and 70 during Infection of a Human Endometrial Epithelial Cell Line In Vitro

“…Subsequent studies revealed that the early release of chlamydial antigens from the inclusion could be increased by the lipophilic microbicide compound C31G, presumably due to destabilization of the chlamydial inclusion membrane as well as direct removal of LPS from the chlamydial envelope (30). The early release of chlamydial LPS, which fixes complement by both the classical and alternative pathways to generate the potent chemoattractant C5a (10), likely serves as one of the first signals for the marked influx of polymorphonuclear leukocytes, observed in patients with cervicitis and endometritis (14). Further, in the case of LPS, it has been postulated that the altered fluidity of the plasma membrane of the infected epithelial cells may thwart destruction by cytotoxic T cells (27).…”

Characterization of kinetics and target proteins for binding of human complement component C3 to the surface-exposed outer membrane of Chlamydia trachomatis serovar L2

“…Several studies have shown that chlamydiae can activate the complement cascade in fresh serum in vitro (16) and that complement greatly enhances the neutralization of infectiv-* Corresponding author. ity by antibody (13,17).…”