Early complement components enhance neutralization of Chlamydia trachomatis infectivity by human sera

Abstract

Immunoglobulin G in human serum neutralizes chlamydial infectivity in vitro. Complement-intact, C5-depleted, and C8-depleted human serum all have significantly more neutralizing activity than serum heated to inactivate early components of complement. Cobra venom factor, an analog of human C3b, enhances neutralization of antichlamydial immunoglobulin G in the absence of early complement components. Chiamydia trachomatis infects mucous membranes of human eyes and genital tracts and causes chronic inflammation with the following resultant clinical syndromes: trachoma (serovars A, B, Ba, and C); conjunctivitis, urethritis, cervicitis, and pelvic inflammatory disease (serovars D, E, F, G, H, I, J, and K); and lymphogranuloma venerum (serovars Li, L2, and L3) (22). The immunology and pathogenesis of these diseases currently are not well understood. Because C. trachomatis infection induces diverse inflammatory reactions, the concept that chlamydial infection manifests different immunopathologic features has emerged (9, 13). As a step toward examining immune interactions of C. trachomatis with the human host, we have begun to examine the interaction of human antibody and complement with this organism in vitro.

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

“…These results are consistent with previous studies demonstrating that the alternative pathway-mediated neutralization of different C. trachomatis serovars is more efficient than that by the classical pathway, especially at higher serum concentrations (13).…”

“…For example, antibody neutralization of serovar K by heat-inactivated human serum in phagocyte-free medium is augmented only if cobra venom factor, a surrogate for C3, is added. This effect appears to be serovar dependent, as it did not occur with the L2 serovar (14).…”

“…Neutralization of chlamydial infectivity probably occurs both before and after entry into the host cell (4, 20) through a variety of mechanisms, some of which are complement dependent.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). Although complement is activated by EBs in the absence of antibody, it does not neutralize chlamydiae without specific antibody as it does other "serum-sensitive" gram-negative bacteria (9).…”

An Ancient Molecular Arms Race: Chlamydia vs. Membrane Attack Complex/Perforin (MACPF) Domain Proteins

“…These data raise the possibility that C5b-C8 recruitment of C9 and pore formation may lead to fatal disruption of the chlamydial envelope; yet, formation of the MAC appears to be dispensable as a primary control mechanism for Chlamydia infections. Depletion of factors C5 and C8 from serum had no effect on in vitro anti-chlamydial activity (24). Additionally, C. muridarum shedding and ascension into the upper genital tract was not impacted in C5-deficient mice (29).…”

“…Complement activation clearly occurs during chlamydial infection with the antibody-independent alternative pathway playing a major role (21). Multiple studies using a tissueculture infection model have demonstrated that Chlamydia inclusion formation is significantly inhibited when EBs are pre-incubated with normal human sera (21)(22)(23)(24)(25) indicating complement factors may be important for controlling infection.…”