Nontuberculous Mycobacteria, Macrophages, and Host Innate Immune Response

Abstract

Although nontuberculous mycobacteria (NTM) are considered opportunistic infections, incidence and prevalence of NTM infection are increasing worldwide becoming a major public health threat. Innate immunity plays an essential role in mediating the initial host response against these intracellular bacteria. Specifically, macrophages phagocytose and eliminate NTM and act as antigen-presenting cells, which trigger downstream activation of cellular and humoral adaptive immune responses. Identification of macrophage receptors, mycobacterial ligands, phagosome maturation, autophagy/necrosis, and escape mechanisms are important components of this immunity network. The role of the macrophage in mycobacterial disease has mainly been studied in tuberculosis (TB), but limited information exists on its role in NTM. In this review, we focus on NTM immunity, the role of macrophages, and host interaction in NTM infection.

Keywords: innate immune response; intracellular pathogen; macrophages; mycobacteria; nontuberculous infection.

FIG 1

Phagocytosis. Pattern recognition receptors (PRRs) are shown in two main districts, C-type lectin receptors (CLR), such as Destin-1 and Dectin-2, and TLRs. MyD88 is a key responsible factor for the downstream signaling cascade of TLRs, which leads to nuclear factor kappa B (NF-κB) activation and ends in the production of inflammatory cytokines (29, 56). Mycobacterial phagocytosis and phagosome maturation through the accumulation of v-ATPase end in the formation of the phagolysosome and mycobacterial killing (29). Macrophage autophagy (autophagolysosome formation) is also an intracellular mycobacterial killing mechanism.