title: 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(-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.
authors: 1] Obesity Immunology Group, Education and Research Centre, St Vincent's University Hospital, University College Dublin, Dublin, Ireland [2] Department of Endocrinology, St Columcille's Hospital, Health Service Executive, Loughlinstown, Dublin, Ireland.
authors: D
authors: D
authors: O'Shea
authors: M
authors: M
authors: Corrigan
authors: M R
authors: MR
authors: Dunne
authors: R
authors: R
authors: Jackson
authors: C
authors: C
authors: Woods
authors: G
authors: G
authors: Gaoatswe
authors: P N
authors: PN
authors: Moynagh
authors: J
authors: J
authors: O'Connell
authors: A E
authors: AE
authors: Hogan
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D005434:Flow Cytometry; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007136:Immunoglobulins / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009767:Obesity, Morbid / Q000150:complications / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D013745:Tetanus Toxoid; D000097802:CD83 Antigen