Complement C3 opsonization of Chlamydia trachomatis facilitates uptake in human monocytes

Abstract

Chlamydia trachomatis is an obligate intracellular bacterium that causes severe infections, which can lead to infertility and ectopic pregnancy. Although both innate and adaptive immune responses are elicited during chlamydial infection the bacterium succeeds to evade host defense mechanisms establishing chronic infections. Thus, studying the host-pathogen interaction during chlamydial infection is of importance to understand how C. trachomatis can cause chronic infections. Both the complement system and monocytes play essential roles in anti-bacterial defense, and, therefore, we investigated the interaction between the complement system and the human pathogens C. trachomatis D and L2. Complement competent serum facilitated rapid uptake of both chlamydial serovars into monocytes. Using immunoelectron microscopy, we showed that products of complement C3 were loosely deposited on the bacterial surface in complement competent serum and further characterization demonstrated that the deposited C3 product was the opsonin iC3b. Using C3-depleted serum we confirmed that complement C3 facilitates rapid uptake of chlamydiae into monocytes in complement competent serum. Complement facilitated uptake did not influence intracellular survival of C. trachomatis or C. trachomatis-induced cytokine secretion. Hence, C. trachomatis D and L2 activate the complement system leading to chlamydial opsonization by iC3b and subsequent phagocytosis, activation and bacterial elimination by human monocytes.

Immunobiology of monocytes and macrophages during Chlamydia trachomatis infection

“…trachomatis is opsonized by the complement C3 fragment iC3b which is recognized by CR3 expressed on monocytes and macrophages [58,59]. We recently demonstrated that complement C3 facilitates rapid uptake of C. trachomatis in human monocytes supporting the role for CR3 in chlamydial uptake, [59].…”

“…trachomatis is opsonized by the complement C3 fragment iC3b which is recognized by CR3 expressed on monocytes and macrophages [58,59]. We recently demonstrated that complement C3 facilitates rapid uptake of C. trachomatis in human monocytes supporting the role for CR3 in chlamydial uptake, [59]. After macrophage entry C. trachomatis can induce a state of persistency, where the bacterium is viable and metabolic active, but does not replicate [1,22,63].…”

“…It appears that serovar L2 can maintain its infectious potency during monocyte infection, because lysates from L2-infected monocytes induce inclusion formation in HeLa cells [53,65]. Nonetheless, we recently demonstrated that C. trachomatis L2 were unable to maintain its infectious and growth potential after 24 hours of incubation within monocytes [59]. Different infection/incubation protocols are likely to cause these discrepancies.…”

Opsonophagocytosis of Chlamydia pneumoniae by Human Monocytes and Neutrophils

“…Grids were blotted dry on filter paper and investigated using a Jeol 1010 transmission electron microscope (Jeol, Tokyo, Japan). Gold deposition was quantified as previously described (47). Briefly, a minimum of seven random fields were imaged for each grid containing at least 12 chlamydial organisms in total.…”

“…Western blotting. SDS-PAGE and Western blotting were performed essentially according to Lausen et al (47). Briefly, purified C. pneumoniae EBs were incubated in 50% serum for 30 min at 37°C, and unbound complement was removed by washing three times in PBS, with centrifugation at 15,000 ϫ g for 15 min between each wash.…”