Sera contributing to mycobacterial growth restriction in vitro display enhanced Fc-mediated phagocytosis

Tuberculosis (TB) remains a major cause of global mortality. Understanding the underlying immune response to the pathogen, <i>Mycobacterium tuberculosis (Mtb)</i>, is essential for the development of vaccines. Evidence is accumulating supporting a contribution of innate immune cells and antibodies in <i>Mtb</i> control. Here, we focus on the functional capacity of antibodies from individuals with TB disease, both before and after TB treatment, individuals with TB infection, and healthy uninfected individuals, using an adapted <i>in vitro</i> mycobacterial growth inhibition assay, measuring Bacillus Calmette-Guérin <b>(</b>BCG) growth inhibition. Sera displayed heterogeneous impact on mycobacterial growth control. This was correlated with enhanced phagocytic capacity, which was abrogated by blocking Fc receptors (FcR) and depletion of antibodies. This phenotype negatively associated with mono- and digalactosylated Fc-glycans of IgG. Together, we demonstrate disease state independent direct effects of sera to mycobacterial growth control and antibody-FcR interactions modulating phagocytic capacity.