Obesity drives dysregulation in DC responses to viral infection

Obesity is a worldwide epidemic, with over 1 billion people worldwide living with obesity. It is associated with an increased risk of over 200 chronic co-morbidities, including an increased susceptibility to infection. Numerous studies have highlighted the dysfunction caused by obesity on a wide range of immune cell subsets, including dendritic cells (DCs). DCs are innate immune sentinels that bridge the innate and adaptive immune systems. DCs provide critical signals that instruct and shape the immune response. Our group has previously reported that DCs from people with obesity display defective cytokine production; however, the mechanisms underpinning these defects are unclear.

We investigated the functional responses of DCs using a murine-specific single-stranded RNA virus, Sendai virus, in mice on a standard diet and in a model of diet-induced obesity.

Here, we demonstrate that GM-CSF cultured bone marrow-derived DCs (GM-DCs) from mice on a high-fat diet (HFD) have reduced cytokine production following viral challenge. This was associated with a dysfunctional metabolism through reduced translation in the HFD GM-DCs.

We propose that obesity-mediated effects on DCs have downstream consequences on their ability to effectively mediate subsequent immune responses, especially during viral infection.