Battling Bacteria That Get Under the Skin

A subset of skin-resident immune cells secrete the protein VEGFα to help mount a robust response to bacterial invasion.

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As the primary barrier between the human body and the environment, our skin is exposed to millions of microbes daily, some of which can cause infection. Like gatekeepers to a fortress, the immune system must mount an appropriate response to bacterial invaders.

A*STAR researchers led by Florent Ginhoux at the Singapore Immunology Network (SIgN) have now discovered how a minor subset of immune cells, called conventional dendritic cells (cDCs), play a key role in fighting off skin infections such as Propionibacterium acnes (P. acnes), which are responsible for outbreaks of acne.

“cDCs are the sentinels of the immune system in all tissues, including the skin. They are the first line of defense against pathogens and hence play crucial roles at all stages of the immune response,” said Ginhoux.

Although skin-resident cDCs are known to be activated in response to danger signals generated upon skin infection, the downstream actions of their activation remained unclear.

In this study, Ginhoux’s team profiled the immune cell populations that accumulate over time in mice whose ears had been injected with P. acnes. They found that a type of cDC, called cDC1, helps recruit neutrophils—another group of immune cells—from the blood to the skin, thereby fortifying the immune response against infection. Probing deeper, the researchers used single-cell mRNA sequencing to reveal that cDC1 could be further categorized into two subgroups, one of which had elevated expression of a protein called VEGFα.

VEGFα is a known attractant for neutrophils, and the specific deletion of the VEGFα gene in cDC1 resulted in impaired neutrophil recruitment in response to P. acnes infection in mice. These findings indicate that VEGFα-secreting cDC1 is necessary for mounting an effective immune response to bacterial infection of the skin.

“Since cDC1s can activate neutrophils to control the intensity of the ensuing immune response, we believe that they represent a new and unique cellular target to modulate skin immunity. We could activate them in conditions that require a stronger immune response or inhibit them in conditions that require dampening of immunity,” Ginhoux explained. For example, targeting VEGFα could offer a new therapeutic window for skin autoimmune diseases such as psoriasis or atopic dermatitis, he said.

Going forward, Ginhoux’s team intends to explore if cDC1 has similar functions in other kinds of human skin infections, or where neutrophils’ recruitment to tissue plays a crucial role in a protective or harmful immune response.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN) and the Skin Research Institute of Singapore (SRIS). The work was done in collaboration with industry partner Nestlé Skin Health R&D/GALDERMA.