Scientists have just made two major discoveries about a harmless bacterium, Staphylococcus epidermidis, present on our skin. A first study identifies the skin as a compartment able to develop highly protective antibody responses to skin colonizing microbe in the absence of inflammation or lymph node contribution. A second study concerns the development of a topical vaccine that can be applied directly to the skin, without the need for a needle or an inflammatory reaction.
Both studies involve Stanford University and the National Institute of Allergy and Infectious Diseases (NIH, Bethesda), including the laboratory led by Prof. Yasmine Belkaid, now President of the Institut Pasteur (Paris).
The skin, an underappreciated organ, is actually an important site for immune defense. Researchers have discovered that the skin is colonized by a harmless bacterium, Staphylococcus epidermidis, which is present on the skin of almost all people. This bacterium has the ability to trigger a strong immune response, leading to the production of antibodies that can prevent infections.
1- Developing the antibody producing machinery in the skin in response to S. epidermidis
A first study conducted by Dr Inta Gribonika in the laboratory of the National Institute of Allergy and Infectious Diseases (NIH, Bethesda) led by Prof. Yasmine Belkaid, now President of the Institut Pasteur (Paris), in collaboration with Stanford University.
In a recent study, Inta Gribonika - a postdoctoral researcher in Prof. Yasmine Belkaid lab -, identifies immune sentinel cells, called Langerhans cells (LCs), as a means of alerting the rest of the immune system to the presence of S. epidermidis on the skin. Upon non-invasive skin painting with this commensal (bacteria from the microbiota), LCs prime humoral response through dermal T cell and B cell activation that leads to long-lived, robust and highly specific antibody production in the skin.
“Observing B cell in the dermal layer of the healthy skin is a novel concept, as up until now skin was thought to be devoid of B cells,” says Inta Gribonika. Not only that, but the antibody production in the skin is achieved in complete absence of inflammation and independently of lymph node contribution and urges us to rethink the classical textbook model of immune response priming. Several key biological concepts are therefore being called into question here.
Observing B cell in the dermal layer of the healthy skin is a novel concept, as up until now skin was thought to be devoid of B cells.
Inta GribonikaPostdoctoral researcher in Prof. Yasmine Belkaid lab
The major finding of Inta and Yasmine’s work is that under these specific circumstances skin can provide all necessary means to form a local dermal tertiary lymphoid structure that is able to support ‘germinal center’ reaction: “It means that a structure in the dermal layer of the skin is able to support machinery for B cell education and differentiation into antibody secreting plasma cells,” explains Inta. Antibodies that are generated through this process are highly protective at controlling topical colonization of bacteria, ensuring the balance and continued diversity of the skin microbiome. These skin-derived antibodies are also highly potent at eliminating systemic infection should the colonizing commensal find its way to breach the cutaneous barrier. “Together, it is a novel and very powerful health insurance mechanism that actively protects the host at all times in health and disease,” emphasizes Yasmine Belkaid.
It is a novel and very powerful health insurance mechanism that actively protects the host at all times in health and disease.
Yasmine BelkaidPresident of the Institut Pasteur
This work uncovers active dialog between skin B cells and microbiota with far-reaching consequences – from better understanding of homeostatic control of host-microbiota interactions, that can work as a platform for innovative vaccinal approaches, to novel clinical applications for the treatment of topical skin diseases. Together, this work opens a door to a new field of skin humoral immunity.
2- Transforming a ubiquitous skin bacterium into a topical vaccine
A second study conducted by Stanford University, in collaboration with the laboratory of the National Institute of Allergy and Infectious Diseases (NIH, Bethesda) led by Prof. Yasmine Belkaid, now President of the Institut Pasteur.
Yasmine and Inta further coauthored another study led by Dr Michael Fischbach’s lab at Stanford University where systemic antibody response to engineered skin commensal is tested in mice as an effective topical vaccination.
Researchers used the bacterium S. epidermidis to create a topical vaccine that can be applied to the skin. They found that applying this bacterium to the skin of mice triggered an immune response similar to that observed in humans. These animal models produced antibodies that protected against infection by tetanus and diphtheria, two serious diseases that can be fatal if left untreated.
The tests showed remarkable efficacy in preventing infection by tetanus and diphtheria. Researchers believe that this approach to vaccination could be used to prevent a wide range of diseases, including viruses, bacteria, fungi, and parasites.
This discovery opens up new possibilities for the prevention of infectious diseases and could revolutionize the way we protect ourselves against pathogens. Researchers hope that this approach to vaccination can be tested in humans in the coming years.
Sources
1- Skin autonomous antibody production regulates host-microbiota interactions, Gribonika I et al., Nature. 11 décembre 2024. doi: 10.1038/s41586-024-08376-y.
2- Discovery and engineering of the antibody response to a prominent skin commensal, Djenet Bousbaine et al., Nature, 11 décembre 2024. doi: 10.1038/s41586-024-08489-4
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