Immune System, Skin Microbiome "Complement" One Another, Finds Penn Medicine Study

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Media Contact:Kim Menard | Kim.Menard@uphs.upenn.edu | 215-662-6183August 27, 2013

Researchers from the Perelman School of Medicine at the University of Pennsylvania demonstrate for the first time that the immune system influences the skin microbiome. A new study found that the skin microbiome – a collection of microorganisms inhabiting the human body – is governed, at least in part, by an ancient branch of the immune system called complement. In turn, it appears microbes on the skin tweak the complement system, as well as immune surveillance of the skin. They found that complement may, in part, be responsible for maintaining a diverse set of microbes on our skin and keeping our skin healthy, which could play a role in a host of skin diseases.

Penn researchers Elizabeth Grice, PhD, assistant professor of Dermatology, and John Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Department of Pathology and Laboratory Medicine, published findings in the August 26 issue of the Proceedings of the National Academy of Sciences.

Commensal, non-pathogenic bacteria that live on the skin provide an important service to their host, blocking pathogenic microbes from gaining a foothold, among other functions. In previous research, Grice and colleagues illuminated the great diversity of bacteria living on the  skin using DNA-based sequence analysis of bacterial genes. However, until this study, very little was known about how the immune system influences those populations of bacteria living on the skin. 

The complement system is like a molecular alarm system and first responder, Grice explains. “It leads the counterattack against microbial insult.” The system is an evolutionarily ancient branch of the immune response and a key function is marking microbial and dying host cells for elimination.

Complement also has inflammatory functions, and the team explored the relationship between the signaling of one particular inflammatory protein of the complement cascade, C5aR (the C5a receptor), and the skin microbiome. Their findings highlight a previously unrecognized role for complement on the skin.

The team treated one group of mice with an inhibitor of C5aR, and another with an inactive analog and compared the animals’ skin microbiome before and after treatment, based on DNA sequence analysis. They found  that while the absolute number of microbes on the skin remained unchanged, the population diversity shifts in animals treated with a C5aR inhibitor compared to those who were not, with some groups of organisms increasing in abundance and others petering out.

The team also looked at the impact of C5aR inhibitor treatment on the immune system itself. They found that genes associated with immune surveillance were downregulated in the skin in inhibitor-treated animals, as was the number of immune cells overall.

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