CERTAIN IMMUNE MECHANISMS INVOLVED IN NEONATAL SEPSIS DEVELOPMENT

  • Jelena Vučić Univerzitet u Nišu, Medicinski fakultet, Katedra za pedijatriju, Niš, Srbija
  • Sandra Stanković Medicinski fakultet Univerziteta u Nišu, Klinika za pedijatriju, UKC Niš, Srbija
  • Karin Vasić Medicinski fakultet Univerziteta u Nišu, Klinika za pedijatriju, UKC Niš, Srbija
Keywords: neonatal sepsis, preterm neonates, immune system, innate immunity

Abstract


Development of neonatal sepsis, especially in preterm neonates, is one of the main factors for high morbidity and mortality in the neonatal period. Preterm neonates, with incompletely matured immune system, have enhanced susceptibility to sepsis development, compared to term infants. Innate immune system activation represents the main protective mechanism, in preterm neonates, against sepsis development. Different components of the innate immune system provide basic protection, as well as they may serve as early biomarkers for neonatal sepsis development. In this review, we analyzed basic mechanisms of innate immune response to pathogen presence and different markers included in the initiation of the inflammatory process. Better understanding the mechanisms involved in sepsis development may provide earlier prediction of sepsis development and results in more potent therapeutic efficiency.  

References

Biondi EA, Mischler M, Jerardi KE, Statile AM, French J, Evans R, et al. Pediatric Research in Inpatient Settings (PRIS) Network. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr 2014; 168(9): 844-9. [CrossRef] [PubMed]

Caron JE, La Pine TR, Augustine NH, Martins TB, Kumánovics A, Hill HR. Severely depressed interleukin-17 production by human neonatal mononuclear cells. Pediatr Res 2014; 76(6):522–7. [CrossRef] [PubMed]

Chiesa C, Pellegrini G, Panero A, Osborn JF, Signore F, Assumma M, et al. C-reactive protein, interleukin-6, and procalcitonin in the immediate postnatal period: influence of illness severity, risk status, antenatal and perinatal complications, and infection. Clin Chem 2003; 49(1): 60-8. [CrossRef] [PubMed]

Coggins SA, Glaser K. Updates in Late-Onset Sepsis: Risk Assessment, Therapy, and Outcomes. Neoreviews 2022; 23(11): 738-55. [CrossRef] [PubMed]

Daskalakis G, Psarris A, Koutras A, Fasoulakis Z, Prokopakis I, Varthaliti A, et al. Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications. Children (Basel) 2023; 10(5): 907. [CrossRef] [PubMed]

Flannery DD, Puopolo KM. Neonatal Early-Onset Sepsis. Neoreviews 2022; 23(11): 756-70. [CrossRef] [PubMed]

Gruber EJ, Leifer CA. Molecular regulation of TLR signaling in health and disease: mechano-regulation of macrophages and TLR signaling. Innate Immun. 2020; 26(1): 15-25. [CrossRef] [PubMed]

Hofer N, Zacharias E, Müller W, Resch B. An update on the use of C-reactive protein in early-onset neonatal sepsis: current insights and new tasks. Neonatology 2012; 102(1):25-36. [CrossRef] [PubMed]

Jenkins-Manning S, Flenady V, Dodd J, Cincotta R, Crowther C. Care of women at risk of preterm birth: a survey of reported practice in Australia and New Zealand. Aust N Z J Obstet Gynaecol 2006; 46(6): 546-8. [CrossRef] [PubMed]

Kai-Larsen Y, Gudmundsson GH, Agerberth B. A review of the innate immune defence of the human foetus and newborn, with the emphasis on antimicrobial peptides. Acta Paediatr 2014; 103(10): 1000-8. [CrossRef] [PubMed]

Koenig JM, Stegner JJ, Schmeck AC, Saxonhouse MA, Kenigsberg LE. Neonatal neutrophils with prolonged survival exhibit enhanced inflammatory and cytotoxic responsiveness. Pediatr Res 2005; 57(3): 424-9. [CrossRef] [PubMed]

Korang SK, Safi S, Nava C, Gordon A, Gupta M, Greisen G, et al. Antibiotic regimens for early-onset neonatal sepsis. Cochrane Database Syst Rev 2021; 5(5): CD013837. [CrossRef] [PubMed]

Lawn JE, Cousens S, Zupan J, Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet 2005; 365(9462): 891-900. [CrossRef] [PubMed]

Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol 2007; 7(5): 379-90. [CrossRef] [PubMed]

Luo H, He J, Qin L, Chen Y, Chen L, Li R, et al. Mycoplasma pneumoniae lipids license TLR-4 for activation of NLRP3 inflammasome and autophagy to evoke a proinflammatory response. Clin Exp Immunol 2021; 203(1): 66-79. [CrossRef] [PubMed]

Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 2009; 302(13): 1421-8. [CrossRef] [PubMed]

McGreal EP, Hearne K, Spiller OB. Off to a slow start: under-development of the complement system in term newborns is more substantial following premature birth. Immunobiology 2012; 217(2): 176-86. [CrossRef] [PubMed]

Ng PC, Lam HS. Biomarkers for late-onset neonatal sepsis: cytokines and beyond. Clin Perinatol 2010; 37(3): 599–610. [CrossRef] [PubMed]

Ng PC, Li K, Wong RP, Chui K, Wong E, Li G, et al. Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections. Arch Dis Child Fetal Neonatal Ed 2003; 88(3): F209-13. [CrossRef] [PubMed]

Pammi M, Flores A, Leeflang M, Versalovic J. Molecular assays in the diagnosis of neonatal sepsis: a systematic review and meta-analysis. Pediatrics 2011; 128(4): e973-85. [CrossRef] [PubMed]

Parra-Llorca A, Pinilla-Gonzlez A, Torrejón-Rodríguez L, Lara-Cantón I, Kuligowski J, Collado MC, et al. Effects of Sepsis on Immune Response, Microbiome and Oxidative Metabolism in Preterm Infants. Children (Basel) 2023; 10(3): 602. [CrossRef] [PubMed]

Raynor LL, Saucerman JJ, Akinola MO, Lake DE, Moorman JR, Fairchild KD. Cytokine screening identifies NICU patients with Gram-negative bacteremia. Pediatr Res 2012; 71(3): 261-6. [CrossRef] [PubMed]

Sadeghi K, Berger A, Langgartner M, Prusa AR, Hayde M, Herkner K, et al. Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling. J Infect Dis 2007; 195(2): 296-302. [CrossRef] [PubMed]

Strunk T, Currie A, Richmond P, Simmer K, Burgner D. Innate immunity in human newborn infants: prematurity means more than immaturity. J Matern Fetal Neonatal Med 2011; 24(1): 25-31. [CrossRef] [PubMed]

van den Berg JP, Westerbeek EA, van der Klis FR, Berbers GA, van Elburg RM. Transplacental transport of IgG antibodies to preterm infants: a review of the literature. Early Hum Dev 2011; 87(2): 67-72. [CrossRef] [PubMed]

van den Brand M, van den Dungen FAM, Bos MP, van Weissenbruch MM, van Furth AM, de Lange A, et al. Evaluation of a real-time PCR assay for detection and quantification of bacterial DNA directly in blood of preterm neonates with suspected late-onset sepsis. Crit Care 2018; 22(1): 105. [CrossRef] [PubMed]

Vance JK, Rawson TW, Povroznik JM, Brundage KM, Robinson CM. Myeloid-Derived Suppressor Cells Gain Suppressive Function during Neonatal Bacterial Sepsis. Int J Mol Sci 2021; 22(13): 7047. [CrossRef] [PubMed]

Vucic J, Vucic M, Stankovic T, Stamenkovic H, Stankovic S, Zlatanovic D. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates. Open Med 2021; 16(1): 139-45. [CrossRef] [PubMed]

Webber RJ, Sweet RM, Webber DS. Circulating Microvesicle-Associated Inducible Nitric Oxide Synthase Is a Novel Therapeutic Target to Treat Sepsis: Current Status and Future Considerations. Int J Mol Sci 2021; 22(24): 13371. [CrossRef] [PubMed]

Wynn JL, Neu J, Moldawer LL, Levy O. Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis. J Perinatol 2009; 29(2): 79-88. [CrossRef] [PubMed]

Yao YM, Osuchowski MF, Wang JH, Pan ZK. Editorial: Immune Dysfunction: An Update of New Immune Cell Subsets and Cytokines in Sepsis. Front Immunol 2021; 12: 822068. [CrossRef] [PubMed]

Published
2026/02/10
Section
Review article