Greasing the inflammatory pathogenesis of viral pneumonias in diabetes.

Type 2 diabetes (T2D) and obesity are independent risk factors for increased morbidity and mortality associated with influenza and SARS-CoV-2 infection. Skewed cellular metabolism shapes immune cell inflammatory responsiveness and function in obesity, T2D, and infection. However, altered immune cell responsiveness and levels of systemic proinflammatory mediators, partly independent of peripheral immune cell contribution, are linked with SARS-CoV-2-associated disease severity. Despite such knowledge, the role of tissue parenchymal cell-driven inflammatory responses, and specifically those dominantly modified in obesity (e.g., adipocytes), in influenza and SARS-CoV-2 infection pathogenesis remain poorly defined. Whether obesity-dependent skewing of adipocyte cellular metabolism uncovers inflammatory clades and promotes the existence of a 'pathogenic-inflammatory' adipocyte phenotype that amplifies SARS-CoV-2 infection diseases severity in individuals with obesity and individuals with obesity and T2D has not been examined. Here, using the knowledge gained from studies of immune cell responses in obesity, T2D, and infection, we highlight the key knowledge gaps underlying adipocyte cellular functions that may sculpt and grease pathogenic processes associated with influenza and SARS-CoV-2 disease severity in diabetes.

Adipocyte inflammation and pathogenesis of viral pneumonias: an overlooked contribution.

Epidemiological evidence establishes obesity as an independent risk factor for increased susceptibility and severity to viral respiratory pneumonias associated with H1N1 influenza and SARS-CoV-2 pandemics. Given the global obesity prevalence, a better understanding of the mechanisms behind obese susceptibility to infection is imperative. Altered immune cell metabolism and function are often perceived as a key causative factor of dysregulated inflammation. However, the contribution of adipocytes, the dominantly altered cell type in obesity with broad inflammatory properties, to infectious disease pathogenesis remains largely ignored. Thus, skewing of adipocyte-intrinsic cellular metabolism may lead to the development of pathogenic inflammatory adipocytes, which shape the overall immune responses by contributing to either premature immunosenescence, delayed hyperinflammation, or cytokine storm in infections. In this review, we discuss the underappreciated contribution of adipocyte cellular metabolism and adipocyte-produced mediators on immune system modulation and how such interplay may modify disease susceptibility and pathogenesis of influenza and SARS-CoV-2 infections in obese individuals.