To explore whether infant mice are more susceptible to microbial infection than adult mice, we infected

both infant and adult mice with live gram-positive Staphylococcus aureus (S. aureus) and monitored the survival rate for at least 14 days. In response to S. aureus challenge, adult mice had an overall survival of 72%, whereas find more infant mice showed a significantly reduced survival rate with 27% surviving to the end of the observation period (p = 0.0114 versus adult mice) (Fig. 1A). Blood samples were collected at different time points post S. aureus challenge from infant and adult mice for proinflammatory cytokine analysis. Although serum peak levels of TNF-α at 2 h and IL-6 at 6 h post S. aureus challenge were slightly lower in infant mice than those in adult mice, they did not reach statistical significances (Fig. 1B). Bacterial counts at 24 h post S. aureus challenge ABT-263 concentration were significantly greater in the blood, liver, and spleen of infant mice compared with adult mice (p < 0.05) (Fig. 1C). At 48 h significantly higher bacterial counts were observed in the blood and all measured visceral organs of infant mice (p < 0.05 versus adult mice) (Fig. 1C). Similar results were also observed in infant mice after being infected with live gram-negative Salmonella typhimurium (S. typhimurium), where a significantly

higher mortality rate (p = 0.0062) (Fig. 1D) and substantial more bacterial counts in the blood and visceral organs (p < 0.05) (Fig. 1F) were evident in infant mice compared with adult mice, whereas serum TNF-α and IL-6 levels were comparable between infant and adult mice (Fig. 1E). We further compared the antimicrobial selleck screening library response between infant and adult mice in a more clinically relevant model of polymicrobial sepsis induced by the cecal slurry method [26]. Infant mice were more susceptible to polymicrobial sepsis with an overall mortality of 76% compared with a

42% mortality rate in adult mice (p = 0.0092) (Fig. 1G). There were no significant differences in the serum TNF-α and IL-6 levels post septic challenge between infant and adult mice (Fig. 1H); however, significantly higher bacterial counts were observed in the blood and visceral organs of infant mice at 12 and 24 h post polymicrobial infection (p < 0.05 versus adult mice) (Fig. 1I). These results indicate that, consistent with an enhanced mortality rate, infant mice exhibit impaired bacterial clearance in response to microbial infection. PMN influx from the circulation into the infectious site during bacterial infection plays a key role in eradicating the invaded microbial pathogens [27]. To ascertain the possible factors responsible for the delayed bacterial clearance observed in infant mice, we measured leukocyte populations in the peritoneal cavity of both infant and adult mice after being challenged with gram-positive or gram-negative bacteria.