Myeloid PTEN inhibits innate host defense during methicillin-resistant <i>Staphylococcus aureus</i>-induced sepsis

Abstract Sepsis is defined as life-threatening organ dysfunction and damage caused by an aberrant host immune response to systemic infection. Due the abundant production of different classes inflammatory mediators, investigating role endogenous proteins that influence multiple signaling pathways might provide important clues in understanding sepsis pathogenesis. Phosphatase tensin homolog (PTEN) a protein/lipid phosphatase, tumor suppressor, negative regulator PI3K/AKT/mTORC pathway. PTEN inhibits FcR-mediated phagocytosis, bacterial killing, expression actions Toll-IL1R (TIR) adaptor MyD88. Whether influences outcome Methicillin-resistant Staphylococcus aureus (MRSA) infection remains be determined. Given pleiotropic effects this phosphatase on both antimicrobial TLR activation, we hypothesize key intermediate perturbs cellular function increases sepsis. Our data showed MRSA increased murine kidney deletion myeloid cells (PTEN Δmyel) decreases loads abscess area compared fl/flmice. Δmyelleads neutrophil but not monocyte/macrophage migration kidney. Furthermore, infected Δmyelshow reduced IL-1β TNF-α In vitro demonstrate −/−macrophages have phagocytosis reactive oxygen species production. These indicate during MRSA-induced sepsis, while decreasing effector functions NIH R01 HL124159-09 T32AI138932-03