a-mouse-model-to-assess-innate-immune-response-to-staphylococcus

A Mouse Model to Assess Innate Immune Response to <em>Staphylococcus aureus</em> Infection

Staphylococcus aureus (S. aureus)&#160;infections, including methicillin resistant stains, are an enormous burden on the healthcare system. With incidence ...

University of California Davis

The immune response to  infection in skin involves the recruitment of polymorphonuclear neutrophils (PMNs) from the bone marrow via the circulation and local granulopoiesis from hematopoietic stem and progenitor cells (HSPCs) that also traffic to infected skin wounds. We focus on regulation of PMN number and function and the role of pore-forming α-toxin (AT), a virulence factor that causes host cell lysis and elicits inflammasome-mediated IL-1β secretion in wounds. Infection with wild-type  enriched in AT reduced PMN recruitment and resulted in sustained bacterial burden and delayed wound healing. In contrast, PMN recruitment to wounds infected with an isogenic AT-deficient  strain was unimpeded, exhibiting efficient bacterial clearance and hastened wound resolution. HSPCs recruited to infected wounds were unaffected by AT production and were activated to expand PMN numbers in proportion to  abundance in a manner regulated by TLR2 and IL-1R signaling. Immunodeficient MyD88-knockout mice infected with  experienced lethal sepsis that was reversed by PMN expansion mediated by injection of wild-type HSPCs directly into wounds. We conclude that AT-induced IL-1β promotes local granulopoiesis and effective resolution of -infected wounds, revealing a potential antibiotic-free strategy for tuning the innate immune response to treat methicillin-resistant  infection in immunodeficient patients.

Article	Year
α-Toxin Regulates Local Granulocyte Expansion from Hematopoietic Stem and Progenitor Cells in Infected Wounds. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 28733486	2017
Is CCR6 Required for the Development of Psoriasiform Dermatitis in Mice? The Journal of investigative dermatology\| PubMed ID: 30193756	2019

Leif S. Anderson

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