CD209 C-Type Lectins Promote Host Invasion, Dissemination, and Infection of Toxoplasma gondii

Abstract

Toxoplasma gondii, the causative agent of toxoplasmosis and a major opportunistic parasite associated with AIDS, is able to invade host cells of animals and humans. Studies suggested that the ability of host invasion by the tachyzoite, the infectious form of T. gondii, is essential for the pathogenicity to promote its dissemination to other parts of animal hosts. However, the detailed molecular mechanisms for host invasion and dissemination of the parasites are not clear. On the other hand, viruses and bacteria are able to interact with and hijack DC-SIGN (CD209) C-type lectin on antigen presenting cells (APCs), such as dendritic cells and macrophages as the Trojan horses to promote host dissemination. In this study, we showed that invasion of T. gondii into host cells was enhanced by this parasite-CD209 interaction that were inhibited by ligand mimickingoligosaccharides and the anti-CD209 antibody. Furthermore, covering the exposures of DC-SIGN by these oligosaccharides reduced parasite burden, host spreading and mortality associated with T. gondii infection. These results suggested that interaction of T. gondii to APCs expressing DC-SIGN might promote host dissemination and infection. Can the blockage of this interaction with Mannan and/or anti-CD209 antibody be developed as a prevention or treatment method for T. gondii infection?

Host F-box protein 22 enhances the uptake of Brucella by macrophages and drives a sustained release of pro-inflammatory cytokines through degradation of the anti-inflammatory effector proteins of Brucella

“…The receptors on macrophages such as Dectin-1, DC-SIGN; and the scavenger receptors, MSR-1 and CD36 are reported to play essential role in the uptake and TLR-independent signaling of various bacterial pathogens (41–43). These receptors are involved in host defense by phagocytosis of various microbial pathogens for intracellular killing (41).…”

“…An enhanced uptake of both Gram positive and Gram negative bacteria have been observed in HeLa cells overexpressing CD36 (42). Various bacterial, protozoan and viral pathogens have been reported to hijack DC-SIGN on dendritic cells and macrophages for host dissemination and pathogenicity (43–48). Studies have demonstrated that NF-κB is required for phagocytosis of bacteria where induction of NF-κB by PAMPS derived from the phagosomal degradation of internalized bacteria could induce the expression of phagocytic receptors (31).…”

C-Type Lectins in Veterinary Species: Recent Advancements and Applications

“…However, not only viruses, but also bacteria and parasites were reported to highjack DC-SIGN or its orthologues, as recently demonstrated for the bacterium Yersinia pestis [ 93 ] and the apicomplexan parasite Toxoplasma gondii [ 94 ]. For the ruminant trematode parasite Fasciola hepatica , a strong downregulation of host DC effector functions via DC-SIGN was observed, finally leading to immune dysregulation and T-cell anergy [ 95 ].…”

“…DC-SIGN can serve as an adhesion and dissemination receptor for cat-born Toxoplasma gondii infection [ 94 ]. Therefore, the specific antibody- or glycan-mediated blocking of paralogues could possibly be applied to prevent toxoplasmosis in chicken [ 123 ], thus reducing the risk of alimentary infections in poultry meat consumers.…”

Vacuolar escape of foodborne bacterial pathogens

“…Intracellular pathogens invade host cells through a variety of mechanisms (Cossart and Helenius, 2014). In professional phagocytes (macrophages, dendritic cells and neutrophils), pathogens can enter via host-driven phagocytosis following binding of the pathogen to pattern recognition receptors such as C-type lectins (Njiri et al, 2020). Moreover, antibodies and complement factors can bind to the pathogen in circulation, through so-called opsonization, allowing the uptake by Fc or complement receptors (Ernst, 1998).…”