Mycobacterial immunevasion - spotlight on the enemy within

Abstract: Mycobacterium avium (Mav) is the medically most important species among the so‐called nontuberculous mycobacteria (NTM). NTM are common inhabitants of the soil, and they are frequent residents on showerhead surfaces.1 Yet, although regular Mav exposure can be assumed to occur, symptomatic infections in immunocompetent people are rare. Thus, in contrast to the more pathogenic M. tuberculosis, Mav is an opportunistic pathogen that mainly affects people with chronic lung disease, for example, those afflicted with cystic fibrosis, young children, and immunocompromised patients.2, 3 Like for all mycobacteria, macrophages are established host cells for Mav, and invasive infections can be associated with impressive granulomas containing specialized macrophages.4 Mav shares other features with M. tuberculosis, such as latency and persistence, which demand complex antibiotic regimens. On the other hand, Mav is particular with respect to its lifestyle and manipulative properties inside macrophages. In contrast to M. tuberculosis and M. marinum, Mav lacks the VII secretion system ESX‐1 (6‐kDa early secretory antigenic target secretion system 1), which mediates pore formation and therefore lysis of cell membranes.5 Complex mechanisms, including secretion of ESAT‐6 (6 kDa early secretory antigenic target) and the activation of host phospholipase A2, allow the translocation of M. tuberculosis from the phagosome to the cytosol.6 Mav has developed other mechanisms to evade the immune response in host macrophages. When phagocytosed by a macrophage, Mav is only partly degraded in phagolysosomes after recognition by TLR 7 and 8. Some bacteria are able to survive in the so‐called Mav compartment (MavC), evading the recognition of the host cell and the herewith associated inflammatory cytokine production (Fig. 1A).7 The intracellular persistence may then facilitate further maintenance and spread of the mycobacteria. This observation spurs the question of how to best tackle these mycobacteria persisting in a less hostile intracellular niche with antibiotics, and maybe adjuvant therapy. Currently, macrolides, rifampicin or rifabutin, and ethambutol constitute the first‐line therapy for NTM lung infections and have to be maintained for at least 12 months. Treatment success with a full clearance of the pathogen is highly variable depending on the antibiotic approach ranging from 32% to 65%.3 However, in up to 60% of pulmonary diseases identification of a Mav is not directly associated with disease progression and spontaneous Mav clearance may occur. Hence the decision for antibiotic treatment remains difficult and is often individualized

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Journal of leukocyte biology. - 109, 1 (2021) , 9-11, ISSN: 1938-3673

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2020
• Urheber: Lößlein, Anne ; Henneke, Philipp

Weitere Informationen

• DOI: 10.1002/jlb.3ce0520-104r
• URN: urn:nbn:de:bsz:25-freidok-1745448
• Rechteinformation: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:49 MEZ