Plk3 Regulates Bacteremia and Supports Sepsis

Abstract

AbstractObjectiveSepsis, which is the body’s response to overwhelming infection, can lead to septic shock, characterized by thrombocytopenia, hypotension, and organ damage. Polo-like kinase 3 (Plk3) is a ubiquitously expressed serine/threonine kinase, but its exact role in immune function is unknown.Approach and ResultsWe usedPlk3−/−and WT mice to evaluate the function of Plk3 in several models of severe sepsis. We found that WT mice die within 48 hours of 100% cecal ligation and puncture (CLP), whilePlk3−/−mice survive. Survival following cecal slurry (CS) injection mirrored that of CLP as recipient WT mice succumbed, while recipientPlk3−/−mice survived. Analysis of bacterial load 24 hours after CLP revealed that WT blood and peritonea were loaded with bacteria, but bacteria were virtually undetectable in the peritonea or blood ofPlk3−/−mice. To determine if bacteria infiltrate the blood ofPlk3−/−mice shortly after infection, we measured bacteria 1 and 3 hours after CS injection. We found a time-dependent increase in bacteria in the blood of WT mice that was not observed inPlk3−/−mice. To determine if the lack of bacteria in the blood ofPlk3−/−mice is due to enhanced clearance, we injectedE. coliIV into WT andPlk3−/−mice. We found 75% mortality for both WT andPlk3−/−mice within 72 hours following IV injection suggesting that survival ofPlk3−/−mice following enteric infection is likely due to reduced bacteremia.ConclusionCollectively our data suggest that Plk3 supports the systemic dissemination of bacteria and subsequent sepsis following enteric infection.