A Protective and Pathogenic Role for Complement During Acute Toxoplasma gondii Infection

Abstract

The infection competence of the protozoan pathogen Toxoplasma gondii is critically dependent on the parasite’s ability to inactivate the host complement system. Toxoplasma actively resists complement-mediated killing in non-immune serum by recruiting host-derived complement regulatory proteins C4BP and Factor H (FH) to the parasite surface to inactivate surface-bound C3 and limit formation of the C5b-9 membrane attack complex (MAC). While decreased complement activation on the parasite surface certainly protects Toxoplasma from immediate lysis, the biological effector functions of C3 split products C3b and C3a are maintained, which includes opsonization of the parasite for phagocytosis and potent immunomodulatory effects that promote pro-inflammatory responses and alters mucosal defenses during infection, respectively. In this review, we discuss how complement regulation by Toxoplasma controls parasite burden systemically but drives exacerbated immune responses locally in the gut of genetically susceptible C57BL/6J mice. In effect, Toxoplasma has evolved to strike a balance with the complement system, by inactivating complement to protect the parasite from immediate serum killing, it generates sufficient C3 catabolites that signal through their cognate receptors to stimulate protective immunity. This regulation ultimately controls tachyzoite proliferation and promotes host survival, parasite persistence, and transmissibility to new hosts.

Protective Immunity Induced by TgMIC5 and TgMIC16 DNA Vaccines Against Toxoplasmosis

“…These results suggest that DNA immunization with TgMIC5 and TgMIC6 can induce considerable protection against acute and chronic T. gondii infection, demonstrating that a cocktail DNA vaccine can trigger a more potent protective immunity than that induced by single antigen-based DNA vaccine (Foroutan et al, 2018). Following natural infection with T. gondii, B cells are activated and specific antibodies are produced (Sikorski et al, 2021). Therefore, efficient humoral responses are of great significance in limiting the spread of T. gondii tachyzoites (Sayles et al, 2000).…”

“…Following natural infection with T. gondii , B cells are activated and specific antibodies are produced ( Sikorski et al., 2021 ). Therefore, efficient humoral responses are of great significance in limiting the spread of T. gondii tachyzoites ( Sayles et al., 2000 ).…”

The Defensive Interactions of Prominent Infectious Protozoan Parasites: The Host’s Complement System

“…During protozoan parasitic infections, the complement system might also be activated by a proteolytic cascade that consequently drives to the opsonization and lysis of invading parasites ( Figure 2 ) [ 12 , 13 ]. It mostly exerts its function through the formation of the MAC and the development of an inflammatory reaction on the parasite´s surface.…”

Four Chemotherapeutic Compounds That Limit Blood-Brain-Barrier Invasion by Toxoplasma gondii

“…The complement system has many important roles, including phagocytizing foreign bodies, clearing immune complexes, and apoptotic cells, and participating in acquired immunity as a part of the innate immune system. Three activation pathways of complement can produce C3 convertase and promote resolution of C3 into the effector molecules C3a and C3b [ 15 ]. C3a is an allergic toxin which can promote an inflammatory response and the proliferation of glial cells.…”