Reduced phagocytic activity of human alveolar macrophages infected with Mycobacterium avium complex

• Published in: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 28; no. 11; pp. 1506 - 1512
• Main Authors: Ikegami, Hiroaki, Yamasaki, Kei, Ogawa, Midori, Nemoto, Kazuki, Akata, Kentaro, Noguchi, Shingo, Fukuda, Kazumasa, Kawanami, Toshinori, Mukae, Hiroshi, Yatera, Kazuhiro
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.11.2022
• Subjects: Macrophage; Mycobacterium avium complex; Nontuberculous mycobacterial lung disease; PBS; CT; Mycobacterium avium complex; CFU; NTM; BALF; Nontuberculous mycobacterial lung disease; MAC; Macrophage; COPD
• ISSN: 1341-321X; 1437-7780
• DOI: 10.1016/j.jiac.2022.07.018

Co-infection of nontuberculous mycobacteria (NTM) with other bacteria is associated with increased frequency of hospitalization and reduced quality of life. However, the clinical significance of co-infection with NTM and other bacteria remains unclear. Here, we investigated the distribution of alveolar macrophage populations, characterized their phagocytic function in bronchoalveolar lavage fluid (BALF), and assessed the bactericidal function of macrophages infected with NTM using cell lines. BALF samples were prospectively obtained from 30 patients with suspected NTM lung disease to evaluate phagocytic activities of macrophages using immunostaining. Bactericidal activities of Staphylococcus aureus (S. aureus) and Mycobacterium intracellulare (M. intracellulare)-infected or -non-infected macrophages were evaluated using macrophage cell lines. Eleven patients with Mycobacterium avium complex (MAC) infection and 19 patients with chronic lower respiratory tract infections except for NTM infection (controls) were enrolled. The percentage of non-polarized (HLA-DR+, CD40−, and CD163−) macrophages in patients infected with MAC was significantly higher than that in controls; non-polarized macrophages demonstrated an impaired ability to phagocytose S. aureus. In vitro experiments revealed higher intracellular S. aureus colony-forming unit counts and proinflammatory cytokine levels in M. intracellulare-infected macrophages than in non-NTM-infected macrophages. Electron microscopy showed morphologically damaged macrophages and M. intracellulare and S. aureus growing in the same phagosome. The proportion of alveolar macrophages (HLA-DR+, CD40−, and CD163−) with impaired phagocytosis increased in MAC-infected individuals. M. intracellulare-infected macrophages reduced bactericidal activity in vitro. Dysfunction of alveolar macrophages may contribute to persistent infection by other bacteria, leading to MAC lung disease progression.