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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
TLR-mediated inflammatory response to neonatal pathogens and co-infection in neonatal immune cells
V Sugitharini1, K Pavani1, A Prema2
1Department of Biotechnology, School of Bio-engineering, SRM University, Kattankulathur, Chennai 603203, India.
Insights
Neonatal immune cells show altered inflammatory responses to common pathogens. Toll-like receptor (TLR) expression and cytokine production differ in cord blood cells compared to adult cells, impacting defense against infections like E. coli.
Area of Science:
- Immunology
- Neonatal Immunity
- Infectious Diseases
Background:
- Neonates rely on innate immunity for pathogen defense.
- Toll-like receptors (TLRs) are crucial for initiating inflammatory responses.
- Common neonatal pathogens include E. coli, Klebsiella pneumoniae, and Staphylococcus aureus, with co-infections frequent.
Purpose of the Study:
- To investigate the Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) mediated inflammatory response in neonates.
- To compare the response of neonatal immune cells to common pathogens with adult immune cells.
Main Methods:
- Mononuclear cells from cord blood (CBMCs) and peripheral blood (PBMCs) were stimulated with lipopolysaccharide (LPS), peptidoglycan (PGN), E. coli, K. pneumoniae, and S. aureus.
- Surface expression of TLR2 and TLR4 on monocyte subpopulations (CD14(+)CD16(+) and CD14(dim)CD16(+)) was analyzed.
- Cytokine levels (IL-6, IL-1β, IL-23, IL-10, IL-13, MCP-1, IL-8) were measured using ELISA and a Human Inflammation Antibody array.
Main Results:
- TLR2 and TLR4 expression varied between monocyte subpopulations in neonatal cells.
- Neonatal cells produced similar levels of IL-6, IL-1β, IL-10, and IL-13 compared to adult cells.
- Neonatal cells showed lower levels of IL-23 and MCP-1, but higher levels of IL-8, compared to adult cells.
- Co-infection with LPS and PGN impaired multiple cytokine productions in cord blood cells.
Conclusions:
- The TLR-mediated inflammatory response to neonatal pathogens is differentially regulated.
- Neonatal immune responses exhibit distinct patterns in cytokine and chemokine production compared to adults.
- Understanding these differences is crucial for managing neonatal sepsis and infections.
Abstract:
Neonates heavily depend on the innate immune system for defence against invading pathogens. Toll-like receptors (TLRs) represent a primary line of host defence and play an important role in orchestrating the inflammatory response to invading pathogens. The most commonly infecting pathogens in neonates are E. coli, Klebsiella pneumoniae and Staphylococcus aureus. Also, co-infection with more than one organism is common in neonatal sepsis. Therefore, we aimed to study the TLR2 and TLR4 mediated neonatal inflammatory response to these pathogens. For this, we stimulated mononuclear cells from cord blood with LPS, PGN, E. coli, K.pneumoniae andS.aureus and analyzed the surface expression of TLR2 and TLR4 on CD14(+)CD16(+) and CD14(dim)CD16(+) and its inflammatory response in comparison with peripheral blood. We found that the TLR2 and TLR4 were differentially expressed on both monocyte subpopulations. Cytokines such as IL-6, IL-1β, IL-23, IL-10, IL-13, MCP-1 and IL-8 were measured using ELISA and we observed that although, neonatal cells were able to produce similar levels of the classical pro-inflammatory (IL-6, IL-1β) and anti-inflammatory (IL-10, IL-13) cytokines as that of adult cells, the amounts of IL-23 and MCP-1 were lower in CBMCs while the chemokine IL-8 was higher in CBMCs when compared with PBMCs. In addition, using Human Inflammation Antibody array technique we found that multiple cytokine production was impaired in cord blood when cells were co-infected with LPS and PGN. In conclusion, the TLR-mediated inflammatory response to neonatal pathogens is differentially regulated by different pathogens.
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