Human Neonatal Peripheral Blood Leukocytes Demonstrate Pathogen-Specific Coordinate Expression of TLR2 TLR4/MD2 and MyD88 During Bacterial Infection In Vivo

摘要

Toll-like receptors (TLRs) play important roles in infection. We have previously reported TLR2 is up-regulated in neonatal Gram-positive (G+) bacteremia whereas TLR4 is up-regulated in neonatal Gram-negative (G−) bacteremia. For functional signaling, TLR4 requires MD-2 and both TLR2 and TLR4 signal need MyD88. However, it is unknown whether newborns can enhance expression of MD-2 and MyD88 with bacterial infection in coordination with TLR expression. We characterized neonatal peripheral blood leukocyte expression of MD-2 and MyD88 in relation to TLR2/4 in newborns. TLR2 mRNA expression by PBMCs and TLR2 protein expression by monocytes/granulocytes were significantly increased in the G+ bacteremia group. TLR4 mRNA on PMBCs and protein expression on monocytes/granulocytes were significantly increased in the G− bacterial group. Remarkably, whereas MyD88 mRNA was increased in all patients with documented bacterial infection and correlated with both TLR2 and TLR4, MD-2 mRNA was selectively increased in G− bacterial group wherein it correlated with TLR4, but not TLR2 mRNA. Our findings demonstrate that during bacterial infection in vivo, newborns selectively and coordinately amplify the TLR2-MyD88 pathway in G+ bacterial infection and the TLR4/MD2/MyD88 pathway in G− bacterial infection, suggesting key roles for innate immune pathway in neonatal responses to bacterial infection.