Autophagy and Host Defense in Nontuberculous Mycobacterial Infection

Abstract

Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens via autophagic machinery. Nontuberculous mycobacteria (NTMs) are ubiquitous microbes, have become increasingly prevalent, and are emerging as clinically important strains due to drug-resistant issues. Compared to Mycobacterium tuberculosis (Mtb), the causal pathogen for human tuberculosis, the roles of autophagy remain largely uncharacterized in the context of a variety of NTM infections. Compelling evidence suggests that host autophagy activation plays an essential role in the enhancement of antimicrobial immune responses and controlling pathological inflammation against various NTM infections. As similar to Mtb, it is believed that NTM bacteria evolve multiple strategies to manipulate and hijack host autophagy pathways. Despite this, we are just beginning to understand the molecular mechanisms underlying the crosstalk between pathogen and the host autophagy system in a battle with NTM bacteria. In this review, we will explore the function of autophagy, which is involved in shaping host-pathogen interaction and disease outcomes during NTM infections. These efforts will lead to the development of autophagy-based host-directed therapeutics against NTM infection.

Keywords: autophagy; host defense; infection; innate immunity; nontuberculous mycobacteria.

Figure 1

A schematic diagram of autophagy regulation by each nontuberculous mycobacterial infection. Green bar depicts the steps of autophagy, including initiation, elongation, maturation, fusion with lysosomes, and degradation. The red box summarizes each NTM response to regulate host autophagy processes. The blue box represents host factors to regulate autophagy during NTM infection. The yellow box shows the effects of autophagy-regulating agents for modulation of autophagy in the context of each NTM infection. The detailed mechanisms have been described in the text.