title: Human neonatal peripheral blood leukocytes demonstrate pathogen-specific coordinate expression of TLR2, TLR4/MD2, and MyD88 during bacterial infection in vivo.
abstract: 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 myeloid differentiation (MD)-2, and both TLR2 and TLR4 signal need myeloid differentiation factor (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 and granulocytes were significantly increased in the G+ bacteremia group. TLR4 mRNA on PMBCs and protein expression on monocytes and granulocytes were significantly increased in the G- bacterial group. Remarkably, although, 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 with 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.
authors.affiliation: Division of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, People's Republic of China.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Ofer
authors.initials: O
authors.lastname: Levy
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
mesh_terms: D001424:Bacterial Infections / Q000097:blood / Q000276:immunology*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007231:Infant, Newborn / Q000097:blood / Q000276:immunology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology*; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
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