In the present study, we demonstrated that infant mice were more susceptible to microbial sepsis. When infected with live bacteria or challenged with a clinically relevant, cecal slurry-induced polymicrobial sepsis, infant mice displayed a significantly higher mortality rate than adult mice. As one of the fundamental functions of the host innate immunity during microbial infection is to rapidly eradicate the invaded pathogens from the body [33], we further examined bacterial

clearance in infant mice after septic challenges. Consistent with an increased susceptibility to microbial sepsis, infant mice showed delayed Selleck C59 wnt and reduced bacterial clearance from the circulation and visceral organs post septic challenges, with significantly higher bacterial counts in the blood, liver, spleen, and lungs compared with adult mice. This defect in bacterial clearance by infant mice is likely to have been underestimated when considering the total amount of bacteria or cecal contents injected between infant and adult mice. Infant mice in response to microbial infection; however, produced comparable proinflammatory cytokines to those of adult mice, which is somewhat discordant with studies in both murine and human neonates [26, 34-36] where significantly

reduced inflammatory cytokines were observed in neonates compared with adults. This discordance might be due to a more matured ability of immune cells to produce inflammatory cytokines in infants compared with neonates. Indeed, other studies have revealed that stimulus-induced production of several inflammatory CT99021 nmr cytokines by neonatal monocytes and APCs is equal to or even exceeds that of adults [37, 38].

These results indicate that, despite an appropriate proinflammatory cytokine production in response to microbial infection in infant mice, the antimicrobial response of their host innate immunity is defective and thus less efficient. Innate phagocytes including Phosphatidylinositol diacylglycerol-lyase PMNs and macrophages form the first line in the host defense against microbial infection. However, in contrast to the well-described deficiencies in adaptive immunity, the innate immune response and in particular the innate phagocyte-associated antimicrobial function in neonates and infants during microbial sepsis remains poorly defined. PMN influx from the circulation into the infectious site plays a key role in eradicating the invaded microbial pathogens [27] and successful clearance of bacterial infection has been shown to rely on a rapid and efficient PMN migration into the infectious site such as peritoneal cavity in several experimentally established murine polymicrobial sepsis models [39-41]. Therefore, a defective and/or reduced recruitment of PMNs into the infectious site may account, at least in part, for the impaired bacterial clearance and increased susceptibility to microbial sepsis observed in infant mice.