Modulating macrophage function to reinforce host innate resistance against Mycobacterium avium complex infection

Abstract

Mycobacterium avium complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental media such as soil as well as in domestic and natural waters. MAC is a primary causative agent of NTM-lung disease that threaten immunocompromised or structural lung disease patients. The incidence and the prevalence of M. tuberculosis infection have been reduced, while MAC infections and mortality rates have increased, making it a cause of global health concern. The emergence of drug resistance and the side effects of long-term drug use have led to a poor outcome of treatment regimens against MAC infections. Therefore, the development of host-directed therapy (HDT) has recently gained interest, aiming to accelerate mycobacterial clearance and reversing lung damage by employing the immune system using a novel adjuvant strategy to improve the clinical outcome of MAC infection. Therefore, in this review, we discuss the innate immune responses that contribute to MAC infection focusing on macrophages, chief innate immune cells, and host susceptibility factors in patients. We also discuss potential HDTs that can act on the signaling pathway of macrophages, thereby contributing to antimycobacterial activity as a part of the innate immune response during MAC infection. Furthermore, this review provides new insights into MAC infection control that modulates and enhances macrophage function, promoting host antimicrobial activity in response to potential HDTs and thus presenting a deeper understanding of the interactions between macrophages and MACs during infection.

Clinical characteristics of patients with non-tuberculous mycobacterial pulmonary disease: a seven-year follow-up study conducted in a certain tertiary hospital in Beijing

“…The DST results indicated that M. abscessus and M. avium were resistant to almost all the anti-TB drugs used in the DST, and over half of the M. intracellulare and M. avium -intracellulare complex isolates were resistant to anti-TB drugs according to DST results. These findings suggest that there is a high prevalence of drug resistance within NTM strains, particularly to KM, CPM, AMK, and PAS ( Gopalaswamy et al., 2020 ; Park et al., 2022 ). Resistance to other commonly used antibiotics like INH and macrolides such as AZM also appears to be relatively high.…”

Intracellular iron accumulation facilitates mycobacterial infection in old mouse macrophages

“…6 A, deferoxamine significantly rescued M. avium killing within old BMMs to a similar level as seen in young BMMs at 24 and 72 h post-infection. M. avium is an intracellular bacteria pathogen that survives within macrophages by blocking phagolysosome maturation, a process that generally destroys invading bacteria [ 12 , 13 ]. This process can be measured by analyzing the colocalization of fluorescent M. avium and LysoTracker dye.…”

“…Upon encountering NTM, macrophages attempt to phagocytose (engulf) the bacteria. However, NTM evolved strategies to manipulate macrophage responses and evade immune detection [ 12 , 13 ]. Some NTM species, such as Mycobacterium avium ( M. avium ), can alter the maturation of the phagosome, hindering lysosomal fusion and thus avoiding exposure to destructive enzymes [ 12 ].…”