Immune protection against septic peritonitis in endotoxin-primed mice is related to reduced neutrophil apoptosis

The innate immune system provides essential information about the presence of infectious danger and signals the activation and instruction of adaptive immunity. The present study addressed the question of whether prior exposu re of the innate immune system to LPS may modulate host defense against acu te septic peritonitis. We show that LPS priming 4 days, but not 2 days, pri or to infection enhances bacterial clearance and improves survival of septi c peritonitis. Immune protection in day 4 LPS-primed mice was specifically associated with a marked increase in the accumulation and activation of neu trophils at the site of infection. Accumulating neutrophils in day 4 LPS-pr imed mice exhibited a normal production of reactive oxygen metabolites in r esponse to in vivo exposure to intestinal bacteria. The local increase in n eutrophil numbers was found to result from a reduced rate of apoptotic cell death. Inhibition of neutrophil apoptosis in LPS-primed mice was mediated by soluble factor(s) distinct from G-CSF and GM-CSF. Thus, engagement of pa ttern recognition systems prior to infection may improve host defense by am plifying the effector cell response of innate immunity. The results also pr ovide in vivo evidence that apoptosis of inflammatory cells represents an i mportant process for the control of host defense to infection.