tetano
Editor, Senior Moderator
Immunity
. 2025 Apr 21:S1074-7613(25)00164-5.
doi: 10.1016/j.immuni.2025.04.001. Online ahead of print. Nerve- and airway-associated interstitial macrophages mitigate SARS-CoV-2 pathogenesis via type I interferon signaling
Stephen T Yeung[SUP] 1 [/SUP], Payal Damani-Yokota[SUP] 1 [/SUP], Sara A Thannickal[SUP] 1 [/SUP], Eric Bartnicki[SUP] 1 [/SUP], Eduardo D Bernier[SUP] 1 [/SUP], Clea R Barnett[SUP] 2 [/SUP], Camille Khairallah[SUP] 1 [/SUP], Ralf Duerr[SUP] 3 [/SUP], Maria G Noval[SUP] 1 [/SUP], Leopoldo N Segal[SUP] 4 [/SUP], Kenneth A Stapleford[SUP] 1 [/SUP], Kamal M Khanna[SUP] 5 [/SUP]
Affiliations
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[SUP]+[/SUP] 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.
Keywords: CD169; MA-10; SARS-CoV-2; Siglec-1; disease tolerance; immunoregulation; immunosuppression; innate immunity; interferons; nerve- and airway-associated interstitial macrophages; tissue-resident macrophages.
. 2025 Apr 21:S1074-7613(25)00164-5.
doi: 10.1016/j.immuni.2025.04.001. Online ahead of print. Nerve- and airway-associated interstitial macrophages mitigate SARS-CoV-2 pathogenesis via type I interferon signaling
Stephen T Yeung[SUP] 1 [/SUP], Payal Damani-Yokota[SUP] 1 [/SUP], Sara A Thannickal[SUP] 1 [/SUP], Eric Bartnicki[SUP] 1 [/SUP], Eduardo D Bernier[SUP] 1 [/SUP], Clea R Barnett[SUP] 2 [/SUP], Camille Khairallah[SUP] 1 [/SUP], Ralf Duerr[SUP] 3 [/SUP], Maria G Noval[SUP] 1 [/SUP], Leopoldo N Segal[SUP] 4 [/SUP], Kenneth A Stapleford[SUP] 1 [/SUP], Kamal M Khanna[SUP] 5 [/SUP]
Affiliations
- PMID: 40286790
- DOI: 10.1016/j.immuni.2025.04.001
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[SUP]+[/SUP] 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.
Keywords: CD169; MA-10; SARS-CoV-2; Siglec-1; disease tolerance; immunoregulation; immunosuppression; innate immunity; interferons; nerve- and airway-associated interstitial macrophages; tissue-resident macrophages.