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Epigenetic Regulation of Leukocyte Inflammatory Mediator Production Dictates Staphylococcus aureus Craniotomy Infection Outcome.
Van Roy, Zachary; Shi, Wen; Kak, Gunjan; Duan, Bin; Kielian, Tammy.
Afiliación
  • Van Roy Z; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE.
  • Shi W; Mary and Dick Holland Regenerative Medicine Program, Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE.
  • Kak G; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE.
  • Duan B; Mary and Dick Holland Regenerative Medicine Program, Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE.
  • Kielian T; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE.
J Immunol ; 211(3): 414-428, 2023 08 01.
Article en En | MEDLINE | ID: mdl-37314520
ABSTRACT
Staphylococcus aureus is a common cause of surgical-site infections, including those arising after craniotomy, which is performed to access the brain for the treatment of tumors, epilepsy, or hemorrhage. Craniotomy infection is characterized by complex spatial and temporal dynamics of leukocyte recruitment and microglial activation. We recently identified unique transcriptional profiles of these immune populations during S. aureus craniotomy infection. Epigenetic processes allow rapid and reversible control over gene transcription; however, little is known about how epigenetic pathways influence immunity to live S. aureus. An epigenetic compound library screen identified bromodomain and extraterminal domain-containing (BET) proteins and histone deacetylases (HDACs) as critical for regulating TNF, IL-6, IL-10, and CCL2 production by primary mouse microglia, macrophages, neutrophils, and granulocytic myeloid-derived suppressor cells in response to live S. aureus. Class I HDACs (c1HDACs) were increased in these cell types in vitro and in vivo during acute disease in a mouse model of S. aureus craniotomy infection. However, substantial reductions in c1HDACs were observed during chronic infection, highlighting temporal regulation and the importance of the tissue microenvironment for dictating c1HDAC expression. Microparticle delivery of HDAC and BET inhibitors in vivo caused widespread decreases in inflammatory mediator production, which significantly increased bacterial burden in the brain, galea, and bone flap. These findings identify histone acetylation as an important mechanism for regulating cytokine and chemokine production across diverse immune cell lineages that is critical for bacterial containment. Accordingly, aberrant epigenetic regulation may be important for promoting S. aureus persistence during craniotomy infection.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Staphylococcus aureus Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Immunol Año: 2023 Tipo del documento: Article País de afiliación: Níger

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Staphylococcus aureus Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Immunol Año: 2023 Tipo del documento: Article País de afiliación: Níger