Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection

Abstract

Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7 ± 7.3 kg m À 2 ), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.

Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials

“…It is possible that DNA vaccines may be more immunogenic in children with their generally lower BMI and should be considered for use in this population. The precise mechanism of how higher BMI affects CD4+ T-cell responses to vaccination is unknown, but obesity has been associated with altered cytokine production, altered monocyte and lymphocyte function, and reduced macrophage and dendritic cell function [37–40]…”

Obesity-related immune responses and their impact on surgical outcomes

“…A recent study has shown that obesity may impact the capacity of dendritic cells (DCs) to mature and to elicit appropriate T-cell responses. 22 These findings may play an important role in mounting effective immune responses in severe obesity potentially linked to an augmented susceptibility to viral infection. Furthermore, excessive nutrient intake "per-se" has been linked to higher amounts of reactive oxygen species (ROS) and reduced mitochondrial oxidative capacity 23 24 .…”

Mucosal‐associated invariant T cells in autoimmunity, immune‐mediated diseases and airways disease

“…For example, adipose tissue is immunologically active and obesity causes a sterile inflammation80 in which iNKT may play an immunoregulatory role 81, 82. MAIT cells may contribute to this inflammation because in human obesity they are enriched in adipose tissue compared with blood, and have a shift towards higher IL‐17 production and reduced IL‐10 secretion 82, 83.…”