Alveolar Macrophages Provide an Early Mycobacterium tuberculosis Niche and Initiate Dissemination

• Published in: Cell host & microbe 2018-09, Vol.24 (3), p.439-446.e4
• Main Authors: Cohen, Sara B., Gern, Benjamin H., Delahaye, Jared L., Adams, Kristin N., Plumlee, Courtney R., Winkler, Jessica K., Sherman, David R., Gerner, Michael Y., Urdahl, Kevin B.
• Format: Article
• Language: English
• Subjects: alveolar macrophages; Animals; Bacterial Proteins - metabolism; ESX-1; granuloma; Granuloma - microbiology; Granuloma - pathology; IL-1; Immunity, Innate - immunology; Inflammation - immunology; innate immunity; lung; Macrophages, Alveolar - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium tuberculosis - immunology; Myeloid Differentiation Factor 88 - metabolism; Pulmonary Alveoli - immunology; Pulmonary Alveoli - microbiology; pulmonary tuberculosis; Receptors, Interleukin-1 - metabolism; Tuberculosis - immunology; Tuberculosis - microbiology
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2018.08.001

Mycobacterium tuberculosis (Mtb) infection is initiated in the distal airways, but the bacteria ultimately disseminate to the lung interstitium. Although various cell types, including alveolar macrophages (AM), neutrophils, and permissive monocytes, are known to be infected with Mtb, the initially infected cells as well as those that mediate dissemination from the alveoli to the lung interstitium are unknown. In this study, using a murine infection model, we reveal that early, productive Mtb infection occurs almost exclusively within airway-resident AM. Thereafter Mtb-infected, but not uninfected, AM localize to the lung interstitium through mechanisms requiring an intact Mtb ESX-1 secretion system. Relocalization of infected AM precedes Mtb uptake by recruited monocyte-derived macrophages and neutrophils. This dissemination process is driven by non-hematopoietic host MyD88/interleukin-1 receptor inflammasome signaling. Thus, interleukin-1-mediated crosstalk between Mtb-infected AM and non-hematopoietic cells promotes pulmonary Mtb infection by enabling infected cells to disseminate from the alveoli to the lung interstitium. [Display omitted] •Early M. tuberculosis infection primarily targets lung alveolar macrophages (AM)•Mtb-infected AM selectively relocalize from the airways to the lung interstitium•AM interstitial localization precedes Mtb dissemination to other immune cell types•Relocalization of infected AM is dependent on Mtb ESX-1 and host IL-1R signaling Using a mouse model, Cohen et al. demonstrate that early Mycobacterium tuberculosis infection predominantly targets alveolar macrophages (AM). Infected AM relocalize from the alveolar space to lung interstitium, preceding bacterial dissemination into migratory myeloid populations. Relocalization requires IL-1R and bacterial ESX-1, highlighting the host-pathogen interplay required to establish infection.