Figure 1. Overview of potential mechanisms and pathways contributing to the infection-resistant phenotype.

Following exposure and infection of the airways and lung parenchyma with Mycobacterium tuberculosis, infection resisters may engage all or a combination of the following mechanisms and pathways to resist infection or rapidly clear infection: (1) airway epithelium defenses: secretion of soluble factors and anti-microbial peptides by airway epithelial cells; (2) macrophage-mediated M. tuberculosis growth restriction: programmed cell death or autophagy (or both) of lung-resident and recruited alveolar macrophages leading to intracellular restriction of M. tuberculosis; (3) innate lymphoid cells (ILCs): production of rapid and effective anti-mycobacterial responses by innate cell populations, including ILCs, mucosal-associated invariant T (MAIT) cells, natural killer (NK) cells, and innate B cells; (4) innate cytokine response: induction of cytokines that directly or indirectly control M. tuberculosis growth in macrophages; (5) trained immunity: molecular reprogramming of monocytes/macrophages leading to enhanced anti-mycobacterial responses; (6) humoral immunity: contribution of differentially glycosylated antibodies in restricting intracellular M. tuberculosis.