Amazing stuff!
"The skin seems to produce its own antibodies to keep microbes in check. ... In mice colonized by Staphylococcus epidermidis, a common and harmless bacterium found on human skin, the skin was able to generate antibodies even when other parts of the immune system were disabled. And this surprise power might be harnessed to fight pathogens: when researchers modified S. epidermidis to display part of the tetanus toxin, the skin response protected mice from a lethal dose."
"The skin — once thought to be a mainly passive barrier — can produce its own antibodies that fight off infections, a pair of studies reports in Nature this week. The findings could pave the way for the development of needle-free vaccines that can be applied to the skin."
"... The initial experiments ... were simple: Dip a cotton swab into a vial containing S. epidermidis. Rub the swab gently on the head of a normal mouse ... and put the mouse back in its cage. Draw blood at defined time points over the next six weeks, asking: Has this mouse’s immune system produced any antibodies that bind to S. epidermidis?
The mice’s antibody response to S. epidermidis was “a shocker,” ...“Those antibodies’ levels increased slowly, then some more – and then even more.” At six weeks, they’d reached a higher concentration than one would expect from a regular vaccination – and they stayed at those levels. ..."
From the abstract (1):
"The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8+ T cell response pre-emptively, in the absence of an infection. However, the scope and purpose of this anti-commensal immune program are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable, and specific antibody response that is conserved in humans and non-human primates. A series of S. epidermidis cell-wall mutants revealed that the cell surface protein Aap is a predominant target.
By colonizing mice with a strain of S. epidermidis in which the parallel β-helix domain of Aap is replaced by tetanus toxin fragment C, we elicit a potent neutralizing antibody response that protects mice against a lethal challenge.
A similar strain of S. epidermidis expressing an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits high antibody titers under conditions of physiologic colonization, including a robust IgA response in the nasal and pulmonary mucosa. Thus, immunity to a common skin colonist involves a coordinated T and B cell response, the latter of which can be redirected against pathogens as a novel form of topical vaccination."
From the abstract (2):
"The microbiota colonizes each barrier site and broadly controls host physiology. However, when uncontrolled, microbial colonists can also promote inflammation and induce systemic infection. The unique strategies employed at each barrier tissue to control the coexistence of the host with its microbiota remain largely elusive. Here we uncover that, within the skin, host-microbiota symbiosis depends on the remarkable ability of the skin to act as an autonomous lymphoid organ. Notably, an encounter with a new skin commensal promotes two parallel responses, both under the control of Langerhans cells.
On one hand, skin commensals induce the formation of classical germinal centers within the lymph node associated with IgG1 and IgG3 antibody responses.
On the other hand, microbial colonization also leads to the development of tertiary lymphoid organs within the skin that can locally sustain IgG2b and IgG2c responses.
These phenomena are supported by the ability of regulatory T cells to convert into T follicular helper cells. Skin autonomous production of antibodies is sufficient to control local microbial biomass, as well as subsequent systemic infection with the same microbe. Collectively, these results reveal a striking compartmentalization of humoral responses to the microbiota allowing for control of both microbial symbiosis and potential pathogenesis."
The skin’s ‘surprise’ power: it has its very own immune system (no public access) "The finding could lead to the development of needle-free vaccines."
Stanford scientists transform ubiquitous skin bacterium into a topical vaccine (original news release) "Findings in mice could translate into a radical, needle-free vaccination approach that would also eliminate reactions including fever, swelling and pain."
Discovery and engineering of the antibody response to a prominent skin commensal (1; no public access, but first article above contains link to PDF, bioRxiv link)
Skin autonomous antibody production regulates host-microbiota interactions (2; no public access, but first article above contains link to PDF)
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