S. aureus is responsible for 76% of all skin and soft tissue infections. Over 20% of the population are carriers in the nasal cavity, and an additional 30% are believed to be transient carriers. Carriage of S. aureus is typically asymptomatic. However, it is important to understand colonization status, particularly in healthcare workers, as they are implicated in the transmission of MRSA.
Despite the clinical importance of MRSA, little is known regarding host mechanisms and how it becomes pathogenic. A limiting factor in study MRSA is the scarity of models for human-bacterial interaction. Therefore, the research team developed a "humanized" mouse model where human skin can be grafted onto mice for in vivo experimentation. Using this model, they studied how healthy adult human skin responds to colonizing MRSA.
The researchers observed transient MRSA colonization of the human stratum corneum over 10 days in the humanized mouse models. This was mediated by local neutrophil response to noninvasive bacteria. IL-8 is the primary immune signal that attracted neutrophils and initiates bacterial killing. This could explain why some people are only transient carriers of MRSA. The data also confirms that high doses of MRSA are needed to induce systemic infection in mouse models.
Using immunohistochemistry, the researchers were able to highlight the dynamic nature of human skin. They used this technique to track the migration of neutrophils through the layers of skin and the unique role that various levels play in colonization and infection.
"The skin is an incredibly dynamic biological environment where immune cells and microbes stand-off against one another to maintain some kind of equilibrium, a fraught peace," says Keira Melican, senior researcher at the Department of Neuroscience, Karolinska Institutet, who led the study. "Breaks in these equilibria typically lead to bad outcomes for humans, and understanding how this process works on the skin could have an impact on how we prevent and treat skin infection in the future."
The vast majority of host-bacterial interactions do not result in infection and studying how healthy human tissue responds to colonizing bacteria will help researchers understand the body keeps these populations in check and could lead to new ways to prevent infection and transmission of pathogens like MRSA.
"We hope that our humanized skin model will help make sure that our results are relevant to humans, and not just mice," says Melican.
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