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

Overview

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.

authors

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

publication date

  • April 21, 2025

Identity

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2025.04.001

PubMed ID

  • 40286790