Psychological stress increases skin infection through the action of TGFβ to suppress immune-acting fibroblasts.

Infections after psychological stress are a major health care problem. Single-cell transcriptomics and lipidomic profiling in a mouse model of stress show that dermal fibroblasts undergoing adipogenesis have defective responses to skin infection. Adrenalectomy or adrenergic inhibition restores the fibroblast adipogenic response to and enables mice to effectively resist infection during stress. Increased susceptibility to from stress is attributed to suppression of the antimicrobial peptide cathelicidin () because adrenaline directly inhibits production by fibroblasts, and mice lacking in fibroblasts do not increase infection after stress. Transforming growth factor β (TGFβ) is induced by stress and adrenergic signaling, and inhibition of TGFβ or deletion of the TGFβ receptor on fibroblasts increases expression and restores protection against infection. Together, these data show that stress initiates a brain-skin axis mediated by TGFβ that impairs the immune defense function of dermal fibroblasts to produce the Camp antimicrobial peptide.