biostudies-literatureCohen SBNICHD NIH HHSNIAID NIH HHSNIHNIGMS NIH HHS439-446.e4https://www.ebi.ac.uk/biostudies/studies/S-EPMC6152889biostudies-literatureUnknown24(3)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.Cell host & microbeAlveolar Macrophages Provide an Early Mycobacterium tuberculosis Niche and Initiate Dissemination.PMC6152889R01 AI134713T32 AI007509T32 HD0072335F32AI1267031K22AI108628-01A1K22 AI108628R01 AI1342461R01AI076327U19 AI1359761R01AI134246T32AI007509-16F32 AI126703U19AI13597U19 AI106761T32 GM007270R01 AI076327Gern BHWinkler JKSherman DRGerner MYCohen SBUrdahl KBDelahaye JLAdams KNPlumlee CRfalseAlveolar Macrophages Provide an Early Mycobacterium tuberculosis Niche and Initiate Dissemination.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.2018-01-01T00:00:00Z2018 Sep2025-04-04T02:29:28.932Z2019-09-24T07:00:52ZS-EPMC61528893014639110.1016/j.chom.2018.08.001