Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms but have become emerging human pathogens worldwide. More than 170 NTM species are reported, and certain species including Mycobacterium avium complex (MAC), M. abscessus complex, and M. kansasii are well-known microbes causing human diseases. A majority of rarely encountered NTM species (~100) have also been reported as clinically relevant human pathogens. NTM lung infections are becoming prevalent in both immunocompetent and immunocompromised individuals. In addition, NTM organisms are causal pathogens of extrapulmonary diseases at lymph nodes, skin, soft tissues, etc. Although NTM infections have been considered to be infected from the environments, recent studies suggest the NTM potentials of zoonotic and person-to-person transmission. Treatment of NTM infections is often extremely complicated from long-term treatment, often challenging due to antibiotic resistance, and unsuccessful. Several host risks factors have been identified and the predisposition includes genetic and acquired immune deficiencies, structural and functional defects of the lungs, geographic distributions, aging, a distinct physical phenotype (low BMI), and sex differences in the context of the increased susceptibility to NTM lung infections. Thus, suggesting the involvement of numerous molecular mechanisms that might be implicated in NTM disease pathogenesis. Understanding the intricate mechanisms in the dialogues between NTMs and host determinants is essential to developing new therapeutic strategies to counteract the disease severity and persistence of NTM infections. However, the detailed molecular mechanisms underlying host-pathogen interactions are poorly understood compared to tuberculosis caused by Mycobacterium tuberculosis.

Recent studies suggest that several virulence factors/components of certain NTMs are responsible for establishing infection in a unique manner. For example, glycopeptidolipids (GPL), individual lipids of NTMs, contribute to biofilm formation and escape from phagolysosomal fusion. In addition, M. ulcerans exotoxin mycolactone-induced autophagy contributes to pathological responses. However, it remains largely unknown how various NTM effectors deploy immune evasion tactics in the host cells to establish the infection. Conversely, host immune arms to NTM species are composed of innate, cell-mediated, and humoral immune pathways. Upon NTM infection, the innate immune signaling pathways are triggered and expanded to enhance host antimicrobial defense or result in immunopathological consequences. The adaptive immune activation with a special focus on Th1 immune responses is one of the critical defense mechanisms by which the host immune system fundamentally manages NTM infection. In addition, several other hosts' molecular regulatory machinery that governs autophagy, immunometabolism, mitochondrial functions, etc., may also closely communicate with host immune pathways during NTM infections. Defining the molecular events that orchestrate host-pathogen interactions is fundamental to understanding the pathogenesis and host defense during NTM diseases.

In this Research Topic, we welcome the submissions of Original Research, Review, and Mini-Review articles focus, but not limited to, the following subtopics:
• how NTM effectors circumvent host defensive pathways through targeting specific host defensive components
• how different NTM or their virulent factors modulate innate immune effectors
• the molecular mechanisms underlying immunopathogenesis in NTM diseases
• adaptive immunity to control or contribute to chronic NTM infection
• autophagy regulation by host and pathogens
• immunometabolism to influence bacterial adaptation to the hosts or to combat NTM pathogenesis
• other biological pathways that affect host protective immunity upon infection
• advances and innovation in the development of new diagnostics and therapeutics against NTM infections

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Frontiers in Immunology

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