The role of complement system and the immune response to tuberculosis infection

Abstract

The complement system orchestrates a multi-faceted immune response to the invading pathogen, Mycobacterium tuberculosis. Macrophages engulf the mycobacterial bacilli through bacterial cell surface proteins or secrete proteins, which activate the complement pathway. The classical pathway is activated by C1q, which binds to antibody antigen complexes. While the alternative pathway is constitutively active and regulated by properdin, the direct interaction of properdin is capable of complement activation. The lectin-binding pathway is activated in response to bacterial cell surface carbohydrates such as mannose, fucose, and N-acetyl-D-glucosamine. All three pathways contribute to mounting an immune response for the clearance of mycobacteria. However, the bacilli can reside, persist, and evade clearance by the immune system once inside the macrophages using a number of mechanisms. The immune system can compartmentalise the infection into a gran-ulomatous structure, which contains heterogenous sub-populations of M. tuberculosis. The granuloma consists of many types of immune cells, which aim to clear and contain the infection whilst sacrificing the affected host tissue. The full extent of the involvement of the complement system during infection with M. tuberculosis is not fully understood. Therefore, we reviewed the available literature on M. tuberculosis and other mycobacterial literature to understand the contribution of the complement system during infection.