Leveraging Antibody, B Cell and Fc Receptor Interactions to Understand Heterogeneous Immune Responses in Tuberculosis

Abstract

Despite over a century of research,Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), continues to kill 1.5 million people annually. Though less than 10% of infected individuals develop active disease, the specific host immune responses that lead toMtbtransmission and death, as well as those that are protective, are not yet fully defined. Recent immune correlative studies demonstrate that the spectrum of infection and disease is more heterogenous than has been classically defined. Moreover, emerging translational and animal model data attribute a diverse immune repertoire to TB outcomes. Thus, protective and detrimental immune responses toMtblikely encompass a framework that is broader than T helper type 1 (Th1) immunity. Antibodies, Fc receptor interactions and B cells are underexplored host responses toMtb. Poised at the interface of initial bacterial host interactions and in granulomatous lesions, antibodies and Fc receptors expressed on macrophages, neutrophils, dendritic cells, natural killer cells, T and B cells have the potential to influence local and systemic adaptive immune responses. Broadening the paradigm of protective immunity will offer new paths to improve diagnostics and vaccines to reduce the morbidity and mortality of TB.