C1q in non-immune human serum has a non-redundant complement function towards clinical Mycobacterium tuberculosis complex strains

Abstract

The Mycobacterium tuberculosis complex (MTBC) includes three human-adapted species: Mycobacterium tuberculosis, Mycobacterium africanum, and Mycobacterium canettii. With their genetic diversity and inherent virulence, these bacteria interact with host factors to influence tuberculosis (TB) transmission and pathogenesis. A critical yet poorly understood aspect of the immune response in TB involves the role of the complement system. Our study aimed to assess the general interaction between the complement system and key clinical MTBC strains representing the principal lineages known to vary in virulence. We found that not only mannose binding lectin (MBL) from the lectin pathway, but also C1q from the classical pathway directly recognize mycobacteria. While MBL generally showed a higher level of binding than C1q, the binding interactions varied across different MTBC strains. We further observed that complement activation products C4b, C3b and the terminal complement complex (TCC) were deposited on the surface of MTBC strains. Inhibition of MBL alone did not substantially alter complement activation, whereas C1q inhibition ceased activation for most strains investigated. Exposure to human serum did not impact the viability or growth of the MTBC strains. In conclusion, both the classical and lectin pathways of complement via C1q and MBL are activated by a broad range of lineages of the MTBC. The classical pathway is the main complement activator in non-immune serum across diverse MTBC lineages, with C1q playing a potentially novel role in the immune response in TB.