TY - JOUR
T1 - The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex
AU - Crilly, Nathan P.
AU - Ayeh, Samuel K.
AU - Karakousis, Petros C.
N1 - Funding Information:
This work was supported by NIH/NIAID grants UH3AI122309 and K24AI143447 to PK. The funders have no role in the content of this manuscript.
Publisher Copyright:
© Copyright © 2021 Crilly, Ayeh and Karakousis.
PY - 2021/1/22
Y1 - 2021/1/22
N2 - Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.
AB - Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.
KW - Mycobacterium avium complex
KW - Mycobacterium tuberculosis
KW - drug repurposing
KW - host-directed therapy
KW - nontuberculous mycobacteria (NTM)
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U2 - 10.3389/fimmu.2020.623119
DO - 10.3389/fimmu.2020.623119
M3 - Review article
C2 - 33552087
AN - SCOPUS:85100529093
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 623119
ER -