title: TLR-mediated inflammatory response to neonatal pathogens and co-infection in neonatal immune cells.
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.
authors.affiliation: Department of Biotechnology, School of Bio-engineering, SRM University, Kattankulathur, Chennai 603203, India.
authors.forename: V
authors.initials: V
authors.lastname: Sugitharini
authors.affiliation: Department of Biotechnology, School of Bio-engineering, SRM University, Kattankulathur, Chennai 603203, India.
authors.forename: K
authors.initials: K
authors.lastname: Pavani
authors.affiliation: Department of Pediatrics, SRM Medical College Hospital and Research Centre, Kattankulathur, Chennai 603203, India.
authors.forename: A
authors.initials: A
authors.lastname: Prema
authors.affiliation: Department of Biotechnology, School of Bio-engineering, SRM University, Kattankulathur, Chennai 603203, India. Electronic address: berlathagam.e@ktr.srmuniv.ac.in.
authors.forename: E
authors.initials: E
authors.lastname: Berla Thangam
mesh_terms: D018925:Chemokines / Q000097:blood; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects / Q000276:immunology*; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007709:Klebsiella / Q000187:drug effects / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D017452:Receptors, IgG / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D017452:Receptors, IgG; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Co-infection; Cytokines; LPS; PGN; TLR