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Publications

Journal Article Ppublish 1 citation

PubMed: 40286790 DOI: 10.1016/j.immuni.2025.04.001

Nerve- and airway-associated interstitial macrophages mitigate SARS-CoV-2 pathogenesis via type I interferon signaling.

Immunity 58(5):1327-1342.e5

Authors: Stephen T Yeung, Payal Damani-Yokota, Sara A Thannickal, Eric Bartnicki, Eduardo D Bernier, Clea R Barnett, Camille Khairallah, Ralf Duerr, Maria G Noval, Leopoldo N Segal, Kenneth A Stapleford, Kamal M Khanna

Affiliations

  • Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Department of Medicine, Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA; Department of Medicine, Vaccine Center, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.

Abstract

Despite vaccines, rapidly mutating viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to threaten human health due to an impaired immunoregulatory pathway and a hyperactive immune response. Our understanding of the local immune mechanisms used by tissue-resident macrophages to safeguard the host from excessive inflammation during SARS-CoV-2 infection remains limited. Here, we found that nerve- and airway-associated interstitial macrophages (NAMs) are required to control mouse-adapted SARS-CoV-2 (MA-10) infection. Control mice restricted lung viral distribution and survived infection, whereas NAM depletion enhanced viral spread and inflammation and led to 100% mortality. Mechanistically, type I interferon receptor (IFNAR) signaling by NAMs was critical for limiting inflammation and viral spread, and IFNAR deficiency in CD169 + macrophages mirrored NAM-depleted outcomes and abrogated their expansion. These findings highlight the essential protective role of NAMs in regulating viral spread and inflammation, offering insights into SARS-CoV-2 pathogenesis and underscoring the importance of NAMs in mediating host immunity and disease tolerance.

MeSH

Sars-Cov-2, Macrophages, Immunity, Interferon Type I, Immunity, Innate, Severe Acute Respiratory Syndrome-Related Coronavirus, Immunosuppression Therapy, Infections