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.
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Abbreviations
- G−:
-
Gram-negative
- G+:
-
Gram-positive
- MD-2:
-
myeloid differentiation protein-2
- MFI:
-
mean fluorescence intensity
- MyD88:
-
myeloid differentiation 88
- PAMPs:
-
pathogen-associated molecular patterns
- PBMCs:
-
peripheral blood mononuclear cells
- PRRs:
-
pattern recognition receptors
- TLRs:
-
toll-like receptors.
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Acknowledgements
We thank the patients and their families for their participation in this study. We thank Liat Stoler-BarakZhiheng Huang and Jianguo Zhou for assistance with data analysis.
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Supported by Chinese Education Ministry 211 Project and the New Teacher Foundation of the Ministry of Education of China (20090071120078); Children's Hospital of Fudan University. O.L. is supported by a Grant NIH RO1 AI067353-01A1 and by the Bill & Melinda Gates Foundation.
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Zhang, JP., Yang, Y., Levy, O. et al. Human Neonatal Peripheral Blood Leukocytes Demonstrate Pathogen-Specific Coordinate Expression of TLR2, TLR4/MD2, and MyD88 During Bacterial Infection In Vivo. Pediatr Res 68, 479–483 (2010). https://doi.org/10.1203/PDR.0b013e3181f90810
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DOI: https://doi.org/10.1203/PDR.0b013e3181f90810
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