The melanocortin-1 receptor (MC1R) is crucially involved in skin melanin pigmentation in many vertebrate species. It binds neuropeptides like alpha-melanocyte-stimulating hormone with with high affinity. However, the role of MC1R in cutaneous infection has not been investigated to the best of our knowledge. Here, we examined the impact of MC1R deficiency in a mouse model for cutaneous infection. MC1R signaling-deficient mice (Mc1re/e) and control mice (C57BL/6) were intradermally infected with 107 colony forming units of S. aureus (strain SH100). The extent of skin infection was monitored for 6 days. Interestingly, Mc1r e/e mice developed larger skin lesions compared with control mice. Gram staining revealed higher bacterial amounts in lesional skin of Mc1re/e mice than in control mice. In accordance with this mRNA expression of nusA and sigA, two established markers for S. aureus, was markedly increased in Mc1re/e mice. Surprisingly, the cutaneous levels of IL-6, IL-8, IL-1β and IL-17a were significantly lower in lesional skin of MC1R signaling-deficient mice than in control mice as determined by real-time RT-PCR analysis. In addition, mRNA expression of Ly6c, Ly6G and CD11b, markers of neutrophils, and subsets of monocytes / macrophages, was decreased in Mc1re/e mice compared with control mice. Using FACS analysis we quantified the number of macrophages in infected skin and found an increased number of macrophages in wild-type mice vs. Mc1r e/e mice. In addition, increased numbers of T regulatory cells were detected in skin lesions of wild-type mice compared with MC1R signaling-deficient mice. In sum, these findings indicate that MC1R is involved in controlling both the extent of infection and subsequent immune response of the skin to S. aureus.

Signal deficiency of melanocortin-1 receptor augments extent of skin infection induced by S. aureus