Mice on a high-fat diet have reduced immunopathology and an altered immune response during respiratory syncytial virus infection

T cells late in infection. HFD mice also had reduced M2 macrophages in the lungs at 7 days post-infection. Notably, HFD mice infected with RSV did not exhibit aberrant proinflammatory cytokine secretion late in infection, as seen with influenza, likely due to effective viral control. In conclusion, HFD mice exhibited reduced disease severity during RSV infection, associated with decreased viral load and an attenuated but sufficient antiviral response. IMPORTANCE: Obesity has been shown to induce dysregulated antiviral responses during influenza infections, resulting in extensive morbidity and mortality. No studies to date have investigated how obesity-induced immune dysregulation affects respiratory syncytial virus (RSV) disease progression. RSV has a high global burden, inflicting millions of infections and tens of thousands of deaths yearly, most notably among the very young, the elderly, and those with comorbidities. It is essential to understand how risk factors, such as obesity, affect disease progression to ensure appropriate protection and care for patients. Here, we demonstrate that male C57BL/6 mice fed a high-fat diet had lower viral loads and attenuated inflammatory responses during RSV infection, resulting in reduced morbidity and immunopathology. This pilot study advances our understanding of how obesity affects pulmonary antiviral immunity to RSV and, concurrently, further elucidates RSV pathogenesis.