tetano
Editor, Senior Moderator
JCI Insight
. 2025 Aug 8;10(15):e194633.
doi: 10.1172/jci.insight.194633. BCG immunization mitigates SARS-CoV-2 replication in macaques via monocyte efferocytosis and neutrophil recruitment in lungs
Mohammad Arif Rahman[SUP] 1 [/SUP], Katherine C Goldfarbmuren[SUP] 2 3 [/SUP], Sarkis Sarkis[SUP] 1 [/SUP], Massimiliano Bissa[SUP] 1 [/SUP], Anna Gutowska[SUP] 1 [/SUP], Luca Schifanella[SUP] 1 [/SUP], Ramona Moles[SUP] 1 [/SUP], Melvin N Doster[SUP] 1 [/SUP], Hanne Andersen[SUP] 4 [/SUP], Yogita Jethmalani[SUP] 5 [/SUP], Leonid Serebryannyy[SUP] 5 [/SUP], Timothy Cardozo[SUP] 6 [/SUP], Mark G Lewis[SUP] 4 [/SUP], Genoveffa Franchini[SUP] 1 [/SUP]
Affiliations
Exposure to Bacillus Calmette-Guérin (BCG) or Canarypox ALVAC/Alum vaccine elicits pro- or antiinflammatory innate responses, respectively. We tested whether prior exposure of macaques to these immunogens protected against SARS-CoV-2 replication in lungs and found more efficient replication control after the pro-inflammatory immunity elicited by BCG. The decreased virus level in lungs was linked to early infiltrates of classical monocytes producing IL-8 with systemic neutrophils, Th2 cells, and Ki67+CD95+CD4+ T cells producing CCR7. At the time of SARS-CoV-2 exposure, BCG-treated animals had higher frequencies of lung infiltrating neutrophils and higher CD14+ cells expressing efferocytosis marker MERTK, responses correlating with decreased SARS-CoV-2 replication in lung. At the same time point, plasma IL-18, TNF-α, TNFSF-10, and VEGFA levels were also higher in the BCG group and correlated with decreased virus replication. Finally, after SARS-CoV-2 exposure, decreased virus replication correlated with neutrophils producing IL-10 and CCR7 preferentially recruited to the lungs of BCG-vaccinated animals. These data point to the importance of the spatiotemporal distribution of functional monocytes and neutrophils in controlling SARS-CoV-2 levels and suggest a central role of monocyte efferocytosis in curbing replication.
Keywords: COVID-19; Immunology; Infectious disease; Innate immunity; Vaccines.
. 2025 Aug 8;10(15):e194633.
doi: 10.1172/jci.insight.194633. BCG immunization mitigates SARS-CoV-2 replication in macaques via monocyte efferocytosis and neutrophil recruitment in lungs
Mohammad Arif Rahman[SUP] 1 [/SUP], Katherine C Goldfarbmuren[SUP] 2 3 [/SUP], Sarkis Sarkis[SUP] 1 [/SUP], Massimiliano Bissa[SUP] 1 [/SUP], Anna Gutowska[SUP] 1 [/SUP], Luca Schifanella[SUP] 1 [/SUP], Ramona Moles[SUP] 1 [/SUP], Melvin N Doster[SUP] 1 [/SUP], Hanne Andersen[SUP] 4 [/SUP], Yogita Jethmalani[SUP] 5 [/SUP], Leonid Serebryannyy[SUP] 5 [/SUP], Timothy Cardozo[SUP] 6 [/SUP], Mark G Lewis[SUP] 4 [/SUP], Genoveffa Franchini[SUP] 1 [/SUP]
Affiliations
- PMID: 40779451
- PMCID: PMC12333941
- DOI: 10.1172/jci.insight.194633
Exposure to Bacillus Calmette-Guérin (BCG) or Canarypox ALVAC/Alum vaccine elicits pro- or antiinflammatory innate responses, respectively. We tested whether prior exposure of macaques to these immunogens protected against SARS-CoV-2 replication in lungs and found more efficient replication control after the pro-inflammatory immunity elicited by BCG. The decreased virus level in lungs was linked to early infiltrates of classical monocytes producing IL-8 with systemic neutrophils, Th2 cells, and Ki67+CD95+CD4+ T cells producing CCR7. At the time of SARS-CoV-2 exposure, BCG-treated animals had higher frequencies of lung infiltrating neutrophils and higher CD14+ cells expressing efferocytosis marker MERTK, responses correlating with decreased SARS-CoV-2 replication in lung. At the same time point, plasma IL-18, TNF-α, TNFSF-10, and VEGFA levels were also higher in the BCG group and correlated with decreased virus replication. Finally, after SARS-CoV-2 exposure, decreased virus replication correlated with neutrophils producing IL-10 and CCR7 preferentially recruited to the lungs of BCG-vaccinated animals. These data point to the importance of the spatiotemporal distribution of functional monocytes and neutrophils in controlling SARS-CoV-2 levels and suggest a central role of monocyte efferocytosis in curbing replication.
Keywords: COVID-19; Immunology; Infectious disease; Innate immunity; Vaccines.