tetano
Editor, Senior Moderator
J Clin Invest
. 2025 Jun 10:e188342.
doi: 10.1172/JCI188342. Online ahead of print. B cell deficiency induces cytotoxic memory CD8+ T cells during influenza-associated bacterial pneumonia
Leigh M Miller[SUP] 1 [/SUP], Alexis M Duray[SUP] 1 [/SUP], Ellyse M Cipolla[SUP] 1 [/SUP], Flavia Rago[SUP] 1 [/SUP], Brooke P Dresden[SUP] 1 [/SUP], Kristen L Parenteau[SUP] 1 [/SUP], Abhigya Gupta[SUP] 2 [/SUP], John F Alcorn[SUP] 1 [/SUP]
Affiliations
Influenza-associated bacterial super-infections in the lung lead to increased morbidity and mortality. Nearly all people have pre-existing memory to influenza virus, which can protect against subsequent infection in the lung. This study explored the role B cells play in protection against bacterial (Staphylococcus aureus or Klebsiella pneumoniae) super-infection with previous heterotypic influenza memory. B cell deficiency resulted in an increased inflammatory lung environment and lung tissue injury during super-infection. Loss of B cells increased populations of memory CD8+ T cells in the lung and these CD8+ T cells were transcriptionally and functionally distinct from WT mice. Use of antibody-deficient mouse models showed that this phenotype was specifically due to loss of antibody production from B cells. Passive immunization with influenza-antibody serum in B cell deficient mice rescued the CD8+ T cell phenotype. CD8+ T cell depletion and lethal super-infection challenge experiments showed that the cytotoxic memory CD8+ T cells from B cell deficient mice protect against super-infection bacterial burden and mortality. These findings provide insight into the importance of B cells for regulating immune responses against infection.
Keywords: Adaptive immunity; Immunology; Infectious disease; Influenza; T cells.
. 2025 Jun 10:e188342.
doi: 10.1172/JCI188342. Online ahead of print. B cell deficiency induces cytotoxic memory CD8+ T cells during influenza-associated bacterial pneumonia
Leigh M Miller[SUP] 1 [/SUP], Alexis M Duray[SUP] 1 [/SUP], Ellyse M Cipolla[SUP] 1 [/SUP], Flavia Rago[SUP] 1 [/SUP], Brooke P Dresden[SUP] 1 [/SUP], Kristen L Parenteau[SUP] 1 [/SUP], Abhigya Gupta[SUP] 2 [/SUP], John F Alcorn[SUP] 1 [/SUP]
Affiliations
- PMID: 40493422
- DOI: 10.1172/JCI188342
Influenza-associated bacterial super-infections in the lung lead to increased morbidity and mortality. Nearly all people have pre-existing memory to influenza virus, which can protect against subsequent infection in the lung. This study explored the role B cells play in protection against bacterial (Staphylococcus aureus or Klebsiella pneumoniae) super-infection with previous heterotypic influenza memory. B cell deficiency resulted in an increased inflammatory lung environment and lung tissue injury during super-infection. Loss of B cells increased populations of memory CD8+ T cells in the lung and these CD8+ T cells were transcriptionally and functionally distinct from WT mice. Use of antibody-deficient mouse models showed that this phenotype was specifically due to loss of antibody production from B cells. Passive immunization with influenza-antibody serum in B cell deficient mice rescued the CD8+ T cell phenotype. CD8+ T cell depletion and lethal super-infection challenge experiments showed that the cytotoxic memory CD8+ T cells from B cell deficient mice protect against super-infection bacterial burden and mortality. These findings provide insight into the importance of B cells for regulating immune responses against infection.
Keywords: Adaptive immunity; Immunology; Infectious disease; Influenza; T cells.