Parenteral BCG vaccine induces lung-resident memory macrophages and trained immunity via the gut-lung axis.

Autor: Jeyanathan M; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Vaseghi-Shanjani M; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Afkhami S; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Grondin JA; Farncombe Family Digestive Health Research Institute and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada., Kang A; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., D'Agostino MR; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Yao Y; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.; Department of Immunology, Zhejiang University, Zhejiang, China., Jain S; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Zganiacz A; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Kroezen Z; Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada., Shanmuganathan M; Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada., Singh R; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Dvorkin-Gheva A; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Britz-McKibbin P; Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada., Khan WI; Farncombe Family Digestive Health Research Institute and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada., Xing Z; McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada. xingz@mcmaster.ca.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2022 Dec; Vol. 23 (12), pp. 1687-1702. Date of Electronic Publication: 2022 Dec 01.
DOI: 10.1038/s41590-022-01354-4
Abstrakt: Aside from centrally induced trained immunity in the bone marrow (BM) and peripheral blood by parenteral vaccination or infection, evidence indicates that mucosal-resident innate immune memory can develop via a local inflammatory pathway following mucosal exposure. However, whether mucosal-resident innate memory results from integrating distally generated immunological signals following parenteral vaccination/infection is unclear. Here we show that subcutaneous Bacillus Calmette-Guérin (BCG) vaccination can induce memory alveolar macrophages (AMs) and trained immunity in the lung. Although parenteral BCG vaccination trains BM progenitors and circulating monocytes, induction of memory AMs is independent of circulating monocytes. Rather, parenteral BCG vaccination, via mycobacterial dissemination, causes a time-dependent alteration in the intestinal microbiome, barrier function and microbial metabolites, and subsequent changes in circulating and lung metabolites, leading to the induction of memory macrophages and trained immunity in the lung. These data identify an intestinal microbiota-mediated pathway for innate immune memory development at distal mucosal tissues and have implications for the development of next-generation vaccine strategies against respiratory pathogens.
(© 2022. The Author(s).)
Databáze: MEDLINE
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