tetano
Editor, Senior Moderator
Am J Physiol Lung Cell Mol Physiol
. 2026 May 6.
doi: 10.1152/ajplung.00309.2025. Online ahead of print.
Biological Sex Influences Immune Response to Influenza Infection in Juvenile Outbred Mice
Ramakrishna Suresh[SUP] 1 [/SUP], Brydie R Huckestein[SUP] 2 [/SUP], Michelle L Manni[SUP] 3 [/SUP], Danielle Antos[SUP] 2 [/SUP], Jason E Shoemaker[SUP] 1 [/SUP], John F Alcorn[SUP] 2 [/SUP]
Affiliations
Children are highly susceptible to influenza virus infection and lung inflammation. The majority of studies of influenza pneumonia in mice are in adult, inbred, same sex mice with limited variation in disease outcomes, unlike what is observed in children. In this study, juvenile outbred mice were challenged with influenza A/California/07/2009 H1N1 virus to examine the temporal effect of infection on lung inflammation in genetically dissimilar male and female mice. In this model, influenza infection induced variable disease severity characterized by viral load, airspace leak and inflammation, and lung function. This response clustered by sex at 3 and 4 days post-infection, but was associated with disease severity by day 8. Influenza virus infection induced altered production of cytokines and chemokines by sex and timing. Males displayed an early cytokine and chemokine response driven by severity; while females showed a late response only in severe mice. This was independent of viral RNA load. Flow cytometry was then conducted to analyze lymphocytes. In male mice, neutrophil recruitment was elevated by disease severity. In contrast, female mice showed increased T cell numbers late in infection regardless of severity. Finally, unsupervised clustering of mice by immune parameters at day 8 showed similarity by sex and severity, with more variability in male mice. These data demonstrate that the immune response to influenza virus infection is impacted by sex and disease severity in pediatric equivalent outbred mice. This complexity of immune activation is important to consider when evaluating drivers of disease pathogenesis or planning therapeutic interventions targeting immune mediators.
Keywords: Cytokine; Lung; Lymphocyte; Pneumonia; Severity.
. 2026 May 6.
doi: 10.1152/ajplung.00309.2025. Online ahead of print.
Biological Sex Influences Immune Response to Influenza Infection in Juvenile Outbred Mice
Ramakrishna Suresh[SUP] 1 [/SUP], Brydie R Huckestein[SUP] 2 [/SUP], Michelle L Manni[SUP] 3 [/SUP], Danielle Antos[SUP] 2 [/SUP], Jason E Shoemaker[SUP] 1 [/SUP], John F Alcorn[SUP] 2 [/SUP]
Affiliations
- PMID: 42090208
- DOI: 10.1152/ajplung.00309.2025
Children are highly susceptible to influenza virus infection and lung inflammation. The majority of studies of influenza pneumonia in mice are in adult, inbred, same sex mice with limited variation in disease outcomes, unlike what is observed in children. In this study, juvenile outbred mice were challenged with influenza A/California/07/2009 H1N1 virus to examine the temporal effect of infection on lung inflammation in genetically dissimilar male and female mice. In this model, influenza infection induced variable disease severity characterized by viral load, airspace leak and inflammation, and lung function. This response clustered by sex at 3 and 4 days post-infection, but was associated with disease severity by day 8. Influenza virus infection induced altered production of cytokines and chemokines by sex and timing. Males displayed an early cytokine and chemokine response driven by severity; while females showed a late response only in severe mice. This was independent of viral RNA load. Flow cytometry was then conducted to analyze lymphocytes. In male mice, neutrophil recruitment was elevated by disease severity. In contrast, female mice showed increased T cell numbers late in infection regardless of severity. Finally, unsupervised clustering of mice by immune parameters at day 8 showed similarity by sex and severity, with more variability in male mice. These data demonstrate that the immune response to influenza virus infection is impacted by sex and disease severity in pediatric equivalent outbred mice. This complexity of immune activation is important to consider when evaluating drivers of disease pathogenesis or planning therapeutic interventions targeting immune mediators.
Keywords: Cytokine; Lung; Lymphocyte; Pneumonia; Severity.