Immune Response Against M. tuberculosis in Human Pulmonary Tuberculosis

Tuberculosis (TB) is an infectious disease that represents a health problem in the world, with pulmonary tuberculosis (TBP) as the most frequent type of TB. This disease is caused by Mycobacterium tuberculosis (M. tuberculosis) that enters the host by inhalation. M. tuberculosis comes into contact with physiological barriers found in the upper respiratory tract (URT) and with innate immunity through airway epithelial cells (AECs). AECs are endowed with innate receptors (TLRs, NOD1, NOD2, NLRP3, TNFR, EGFR, and C-type lectins) that allow them to interact with microorganisms, or their components, and are a source of antimicrobial peptides (AMPs), such as α- defensins, β-defensins, cathelicidin (LL-37/hCAP-18), pro-inflammatory cytokines and chemokines. However, M. tuberculosis can resist and surpass innate defense mechanisms, descend to the lower respiratory tract (LRT) and arrives at the alveoli. At this site, M. tuberculosis comes into contact with alveolar macrophages (AMs), dendritic cells (DCs), type II epithelial cells, and neutrophils. M. tuberculosis interacts with AMs through TLRs (TLR2, TLR4, and TLR9) and triggers the production of proinflammatory (IL-1β, IL-6, TNF-α, IL-12) and anti-inflammatory cytokines (IL-4, IL- 10). Innate immunity includes phagocytosis, killing, cytokines, and chemokines production with the participation of T cells, later, that orchestrate the elimination of mycobacteria. For M. tuberculosis clearance, it is fundamental that AMs or DCs present mycobacterial antigens to T cells and begin an acquired immune response for mycobacterial elimination. During the infection in the alveolar space, there are innate molecules such as AMPs, ROS, NO, pro-inflammatory cytokines (IL-1β, IL-6, IL-12, IL-18, TNF-α and IFN-γ), anti-inflammatory cytokines (IL-4, IL-10 and TGF-β), and immune specific T cells for M. tuberculosis clearance. Control of TB infection has been associated with IFN-γ production by T cells since it triggers and increases bactericidal AMs activity. However, the alveolar immune response against M. tuberculosis may not be effective due to the evasive mechanisms employed by the mycobacteria and the secretion of its virulent factors.

Keywords: Antimicrobial Peptides, Cytokines, Chemokines, M. tuberculosis, Macrophages, Neutrophils, Pulmonary Tuberculosis, Tuberculosis, T cells.