Repeated social defeat activates dendritic cells and enhances Toll-like receptor dependent cytokine secretion.
Stress hormones significantly impact dendritic cell (DC) activation and function, typically in a suppressive fashion. However, a social stressor termed social disruption (SDR) has been shown to induce an increase in inflammatory responses and a state of glucocorticoid resistance in splenic CD11b+ monocytes. These experiments were designed to determine the effects of SDR on DC activation, Toll-like receptor-induced cytokine secretion, and glucocorticoid sensitivity. Compared to cells obtained from control animals, splenic DCs from SDR mice displayed increased levels of MHC I, CD80, and CD44, indicative of an activated phenotype. In addition, DCs from SDR mice produced comparatively higher TNF-alpha, IL-6, and IL-10 in response to in vitro stimulation with LPS and CpG DNA. Increased amounts of TNF-alpha and IL-6 were also evident in SDR DC cultures stimulated with poly(I:C). Furthermore, as shown previously in CD11b+ monocytes, the CD11c+ DCs obtained from SDR mice were glucocorticoid resistant. Taken together, the data suggest that social stress, in the absence of any immune challenge, activates DCs, increases DC cytokine secretion in response to Toll-specific stimuli and renders DCs glucocorticoid resistant.
Section of Oral Biology, College of Dentistry, The Ohio State University, Postle Hall, 305 W. 12th Avenue, Columbus, OH 43210, USA. powell.424@osu.edu
Nicole D
ND
Powell
M T
MT
Bailey
J W
JW
Mays
L M
LM
Stiner-Jones
M L
ML
Hanke
D A
DA
Padgett
John F
JF
Sheridan
D000704:Analysis of Variance; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004291:Dominance-Subordination; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology; D018960:Hyaluronan Receptors / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013315:Stress, Psychological / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018122:B7-1 Antigen; D039481:CD11b Antigen; D039521:CD11c Antigen; D016207:Cytokines; D005938:Glucocorticoids; D018960:Hyaluronan Receptors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10