Changes in peritoneal macrophage composition during sepsis.

Abstract

Abstract Sepsis occurs when an infection activates a systemic inflammatory response. The mortality rate for severe sepsis remains high (30–50%). Additionally, many patients who survive sepsis develop a persistent inflammation, immunosuppression and catabolism syndrome (PICS). Macrophages are early sentinels of infection and exert both beneficial and detrimental functions during sepsis. As phagocytes, they clear pathogens. Macrophages also express pattern recognition receptors, which trigger inflammatory cytokine production. This process plays a key role in host defense; however during sepsis excessive inflammation leads to immune dysregulation and organ dysfunction. Tissue-resident macrophages include diverse populations with heterogeneous cell surface markers and functions. Two populations exist in the peritoneum of mice: large peritoneal macrophages (LPM; CD11b+, F4/80-hi, MHC-II-lo) and small peritoneal macrophages (SPM; CD11b+, F4/80-lo, MHC-II-hi). These subsets exhibit different levels of phagocytosis and cytokine production. Importantly, no prior study has comprehensively examined the migration of monocytes, SPM and LPM during sepsis. We used the mouse cecal ligation and puncture model (CLP) to study this process. Our data demonstrate that LPM exit the peritoneum by 18h post-CLP or sham surgery, accompanied by substantial infiltration of monocytes. Within 14 days after sham surgery, LPM have returned to the peritoneum. In contrast, 14 days after CLP there are still few LPM and a large number of monocytes in the peritoneum. These data indicate that, despite an apparent return to homeostasis, an inflammatory process persists in the peritoneum of these mice. This persisting inflammation may contribute to PICS.