tetano
Editor, Senior Moderator
Mucosal Immunol
. 2023 Sep 18;S1933-0219(23)00070-3.
doi: 10.1016/j.mucimm.2023.09.004. Online ahead of print. Obesity amplifies influenza virus-driven disease severity in male and female mice
Pablo C Alarcon[SUP] 1 [/SUP], Michelle Sma Damen[SUP] 2 [/SUP], Cassidy J Ulanowicz[SUP] 3 [/SUP], Keisuke Sawada[SUP] 1 [/SUP], Jarren R Oates[SUP] 3 [/SUP], Andrea Toth[SUP] 4 [/SUP], Jennifer L Wayland[SUP] 1 [/SUP], Hak Chung[SUP] 2 [/SUP], Traci E Stankiewicz[SUP] 2 [/SUP], Maria E Moreno-Fernandez[SUP] 5 [/SUP], Sara Szabo[SUP] 6 [/SUP], William J Zacharias[SUP] 4 [/SUP], Senad Divanovic[SUP] 7 [/SUP]
Affiliations
Influenza virus-induced respiratory pneumonia remains a major public health concern. Obesity, metabolic diseases, and female sex are viewed as independent risk factors for worsened influenza virus-induced lung disease severity. However, lack of experimental models of severe obesity in female mice limits studies. Here, via utility of thermoneutral housing (TN, 30°C) and high fat diet (HFD) feeding, we induced severe obesity and metabolic disease in female C57BL/6 mice and compared their responses to severely obese male C57BL/6 counterparts during influenza virus infection. We show that lean male and female mice have similar lung edema, inflammation, and immune cell infiltration during influenza virus infection. At standard housing conditions, HFD-fed male, but not female, mice exhibit severe obesity, metabolic disease, and exacerbated influenza disease severity. However, combining TN-housing and HFD feeding in female mice induces severe obesity and metabolic disease, which is sufficient to amplify influenza virus-driven disease severity to a level comparable to severely obese male counterparts. Lastly, increased total body weights of male and female mice at time of infection correlated with worsened influenza virus-driven disease severity metrics. Together, our findings confirm the impact of obesity and metabolic disease as key risk factors to influenza disease severity and present a novel mouse experimental model suitable for mechanistic interrogation of sex, obesity, and metabolic disease traits in influenza virus-driven disease severity.
. 2023 Sep 18;S1933-0219(23)00070-3.
doi: 10.1016/j.mucimm.2023.09.004. Online ahead of print. Obesity amplifies influenza virus-driven disease severity in male and female mice
Pablo C Alarcon[SUP] 1 [/SUP], Michelle Sma Damen[SUP] 2 [/SUP], Cassidy J Ulanowicz[SUP] 3 [/SUP], Keisuke Sawada[SUP] 1 [/SUP], Jarren R Oates[SUP] 3 [/SUP], Andrea Toth[SUP] 4 [/SUP], Jennifer L Wayland[SUP] 1 [/SUP], Hak Chung[SUP] 2 [/SUP], Traci E Stankiewicz[SUP] 2 [/SUP], Maria E Moreno-Fernandez[SUP] 5 [/SUP], Sara Szabo[SUP] 6 [/SUP], William J Zacharias[SUP] 4 [/SUP], Senad Divanovic[SUP] 7 [/SUP]
Affiliations
- PMID: 37730122
- DOI: 10.1016/j.mucimm.2023.09.004
Influenza virus-induced respiratory pneumonia remains a major public health concern. Obesity, metabolic diseases, and female sex are viewed as independent risk factors for worsened influenza virus-induced lung disease severity. However, lack of experimental models of severe obesity in female mice limits studies. Here, via utility of thermoneutral housing (TN, 30°C) and high fat diet (HFD) feeding, we induced severe obesity and metabolic disease in female C57BL/6 mice and compared their responses to severely obese male C57BL/6 counterparts during influenza virus infection. We show that lean male and female mice have similar lung edema, inflammation, and immune cell infiltration during influenza virus infection. At standard housing conditions, HFD-fed male, but not female, mice exhibit severe obesity, metabolic disease, and exacerbated influenza disease severity. However, combining TN-housing and HFD feeding in female mice induces severe obesity and metabolic disease, which is sufficient to amplify influenza virus-driven disease severity to a level comparable to severely obese male counterparts. Lastly, increased total body weights of male and female mice at time of infection correlated with worsened influenza virus-driven disease severity metrics. Together, our findings confirm the impact of obesity and metabolic disease as key risk factors to influenza disease severity and present a novel mouse experimental model suitable for mechanistic interrogation of sex, obesity, and metabolic disease traits in influenza virus-driven disease severity.