Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor

Abstract

African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection.

From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

“…Hence, to be successful, trypanosomes acquired multiple independent methods to circumvent antibody-mediated destruction. Antigenic variation of their surface coat and inhibition of complement-mediated lysis are the main tools employed by trypanosomes to ensure successful development of infection (14,15). In addition, trypanosomes have acquired the capacity to manipulate the host antibody production capacity by directly affecting B cells and plasma cells (PCs) (16)(17)(18)(19).…”

The Elusive <em>Trypanosoma cruzi</em> Disperse Gene Protein Family (DGF-1)

“…An example supporting this idea is the recent discovery that the Trypanosoma brucei invariant protein gp65 (ISG65) is a C3b complement receptor [59]. This receptor is an important part of innate immune system, and its role is central to the activation of the alternative, classical and lectin pathways of complement.…”

The Elusive Trypanosoma cruzi Disperse Gene Protein Family (DGF-1)

“…An example supporting this idea is the recent discovery that the Trypanosoma brucei invariant protein gp65 (ISG65) is a C3b complement receptor [ 60 ]. This receptor is an important part of the innate immune system, and its role is central to the activation of the alternative, classical, and lectin pathways of complement.…”