313
Views
30
CrossRef citations to date
0
Altmetric
Reviews

Toll-like receptor signaling in neonatal sepsis and inflammation: a matter of orchestration and conditioning

&
Pages 1239-1252 | Published online: 10 Jan 2014

References

  • Stoll BJ, Hansen N, Fanaroff AA et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 110(2 Pt. 1), 285–291 (2002).
  • Stoll BJ, Hansen NI, Sanchez PJ et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 127(5), 817–826 (2011).
  • Bersani I, Speer CP. Nosocomial sepsis in neonatal intensive care: inevitable or preventable? Z. Geburtshilfe Neonatol. 216(4), 186–190 (2012).
  • Stoll BJ, Hansen N, Fanaroff AA et al. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N. Engl. J. Med. 347(4), 240–247 (2002).
  • Filias A, Theodorou GL, Mouzopoulou S, Varvarigou AA, Mantagos S, Karakantza M. Phagocytic ability of neutrophils and monocytes in neonates. BMC Pediatrics 11, 29 (2011).
  • Urlichs F, Speer CP. Neutrophil function in preterm and term infants. NeoReviews 5(10), e417–e429 (2004).
  • Wynn JL, Levy O. Role of innate host defenses in susceptibility to early-onset neonatal sepsis. Clin. Perinatol. 37(2), 307–337 (2010).
  • Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat. Rev. Immunol. 7(5), 379–390 (2007).
  • Chelvarajan RL, Collins SM, Doubinskaia IE et al. Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens. J. Leukoc. Biol. 75(6), 982–994 (2004).
  • Levy O, Zarember KA, Roy RM, Cywes C, Godowski PJ, Wessels MR. Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848. J. Immunol. 173(7), 4627–4634 (2004).
  • Angelone DF, Wessels MR, Coughlin M et al. Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-alpha production in vitro and in vivo. Pediatr. Res. 60(2), 205–209 (2006).
  • Weatherstone KB, Rich EA. Tumor necrosis factor/cachectin and interleukin-1 secretion by cord blood monocytes from premature and term neonates. Pediatr. Res. 25(4), 342–346 (1989).
  • Peters AM, Bertram P, Gahr M, Speer CP. Reduced secretion of interleukin-1 and tumor necrosis factor-alpha by neonatal monocytes. Biol. Neonate 63(3), 157–162 (1993).
  • Wilson CB, Westall J, Johnston L, Lewis DB, Dower SK, Alpert AR. Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies. J. Clin. Invest. 77(3), 860–867 (1986).
  • Scott ME, Kubin M, Kohl S. High level interleukin-12 production, but diminished interferon-gamma production, by cord blood mononuclear cells. Pediatr. Res. 41(4 Pt. 1), 547–553 (1997).
  • Peat EB, Augustine NH, Drummond WK, Bohnsack JF, Hill HR. Effects of fibronectin and group B streptococci on tumour necrosis factor-alpha production by human culture-derived macrophages. Immunology 84(3), 440–445 (1995).
  • Berner R, Niemeyer CM, Leititis JU et al. Plasma levels and gene expression of granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 in neonatal early onset sepsis. Pediatr. Res. 44(4), 469–477 (1998).
  • Speer CP. Chorioamnionitis, postnatal factors and proinflammatory response in the pathogenetic sequence of bronchopulmonary dysplasia. Neonatology 95(4), 353–361 (2009).
  • Speer CP. Neonatal respiratory distress syndrome: an inflammatory disease? Neonatology 99(4), 316–319 (2011).
  • Hunter CJ, Upperman JS, Ford HR, Camerini V. Understanding the susceptibility of the premature infant to necrotizing enterocolitis (NEC). Pediatr. Res. 63(2), 117–123 (2008).
  • Nanthakumar N, Meng D, Goldstein AM et al. The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. PLoS ONE, 6(3), e17776 (2011).
  • Volpe JJ. Postnatal sepsis, necrotizing entercolitis, and the critical role of systemic inflammation in white matter injury in premature infants. J. Pediatr. 153(2), 160–163 (2008).
  • Khwaja O, Volpe JJ. Pathogenesis of cerebral white matter injury of prematurity. Arch. Dis. Child Fetal Neonatal Ed. 93(2), F153–F161 (2008).
  • Thomas W, Speer CP. Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome? Neonatology 99(3), 177–187 (2011).
  • Nguyen CN, Schnulle PM, Chegini N, Luo X, Koenig JM. Neonatal neutrophils with prolonged survival secrete mediators associated with chronic inflammation. Neonatology 98(4), 341–347 (2010).
  • Kramer BW, Jobe AH, Ikegami M. Monocyte function in preterm, term, and adult sheep. Pediatr. Res. 54(1), 52–57 (2003).
  • Harju K, Glumoff V, Hallman M. Ontogeny of Toll-like receptors Tlr2 and Tlr4 in mice. Pediatr. Res. 49(1), 81–83 (2001).
  • Groneck P, Speer CP. Inflammatory mediators and bronchopulmonary dysplasia. Arch. Dis. Child Fetal Neonatal Ed. 73(1), F1–F3 (1995).
  • Afrazi A, Sodhi CP, Richardson W et al. New insights into the pathogenesis and treatment of necrotizing enterocolitis: Toll-like receptors and beyond. Pediatr. Res. 69(3), 183–188 (2011).
  • Nathan C. Neutrophils and immunity: challenges and opportunities. Nat. Rev. Immunol. 6(3), 173–182 (2006).
  • Akira S. TLR signaling. Curr. Top Microbiol. Immunol. 311, 1–16 (2006).
  • Chen G, Shaw MH, Kim YG, Nunez G. NOD-like receptors: role in innate immunity and inflammatory disease. Annu. Rev. Pathol. 4, 365–398 (2009).
  • Meylan E, Tschopp J, Karin M. Intracellular pattern recognition receptors in the host response. Nature 442(7098), 39–44 (2006).
  • Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 140(6), 805–820 (2010).
  • Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 449(7164), 819–826 (2007).
  • Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin. Immunol. 19(1), 3–10 (2007).
  • Nishiya T, Kajita E, Miwa S, Defranco AL. TLR3 and TLR7 are targeted to the same intracellular compartments by distinct regulatory elements. J. Biol. Chem. 280(44), 37107–37117 (2005).
  • Takeuchi O, Hoshino K, Kawai T et al. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11(4), 443–451 (1999).
  • Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857), 732–738 (2001).
  • Heil F, Hemmi H, Hochrein H et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303(5663), 1526–1529 (2004).
  • Chuang TH, Lee J, Kline L, Mathison JC, Ulevitch RJ. Toll-like receptor 9 mediates CpG-DNA signaling. J. Leukoc. Biol. 71(3), 538–544 (2002).
  • Fusunyan RD, Nanthakumar NN, Baldeon ME, Walker WA. Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes. Pediatr. Res. 49(4), 589–593 (2001).
  • Chaudhuri N, Whyte MK, Sabroe I. Reducing the toll of inflammatory lung disease. Chest 131(5), 1550–1556 (2007).
  • Sadeghi K, Berger A, Langgartner M et al. Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling. J. Infect Dis. 195(2), 296–302 (2007).
  • Xu Y, Tao X, Shen B et al. Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408(6808), 111–115 (2000).
  • Jenkins KA, Mansell A. TIR-containing adaptors in Toll-like receptor signalling. Cytokine 49(3), 237–244 (2010).
  • Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao Z. MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7(6), 837–847 (1997).
  • Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z. IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J. Biol. Chem. 274(27), 19403–19410 (1999).
  • Takaesu G, Kishida S, Hiyama A et al. TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. Mol. Cell 5(4), 649–658 (2000).
  • Yamamoto M, Takeda K. Current views of toll-like receptor signaling pathways. Gastroenterol. Res. Pract. 2010, 240365 (2010).
  • Karin M, Yamamoto Y, Wang QM. The IKK NF-kappa B system: a treasure trove for drug development. Nat. Rev. Drug Discov. 3(1), 17–26 (2004).
  • Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat. Rev. Immunol. 6(9), 644–658 (2006).
  • Brint EK, Xu D, Liu H et al. ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat. Immunol. 5(4), 373–379 (2004).
  • Burns K, Janssens S, Brissoni B, Olivos N, Beyaert R, Tschopp J. Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J. Exp. Med. 197(2), 263–268 (2003).
  • Naiki Y, Michelsen KS, Zhang W, Chen S, Doherty TM, Arditi M. Transforming growth factor-beta differentially inhibits MyD88-dependent, but not TRAM- and TRIF-dependent, lipopolysaccharide-induced TLR4 signaling. J. Biol. Chem. 280(7), 5491–5495 (2005).
  • Nguyen HA, Rajaram MV, Meyer DA, Schlesinger LS. Pulmonary surfactant protein A and surfactant lipids upregulate IRAK-M, a negative regulator of TLR-mediated inflammation in human macrophages. Am. J. Physiol. Lung Cell. Mol. Physiol. 303(7), L608–L616 (2012).
  • LeBouder E, Rey-Nores JE, Rushmere NK et al. Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk. J. Immunol. 171(12), 6680–6689 (2003).
  • Fukao T, Tanabe M, Terauchi Y et al. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat. Immunol. 3(9), 875–881 (2002).
  • Riva F, Bonavita E, Barbati E, Muzio M, Mantovani A, Garlanda C. TIR8/SIGIRR is an interleukin-1 receptor/toll like receptor family member with regulatory functions in inflammation and immunity. Front. immunol. 3, 322 (2012).
  • Wietek C, Miggin SM, Jefferies CA, O’Neill LA. Interferon regulatory factor-3-mediated activation of the interferon-sensitive response element by Toll-like receptor (TLR) 4 but not TLR3 requires the p65 subunit of NF-kappa. J. Biol. Chem. 278(51), 50923–50931 (2003).
  • Feterowski C, Emmanuilidis K, Miethke T et al. Effects of functional Toll-like receptor-4 mutations on the immune response to human and experimental sepsis. Immunology 109(3), 426–431 (2003).
  • Kawai T, Adachi O, Ogawa T, Takeda K, Akira S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11(1), 115–122 (1999).
  • Poltorak A, He X, Smirnova I et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282(5396), 2085–2088 (1998).
  • Takeuchi O, Hoshino K, Akira S. Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J. Immunol. 165(10), 5392–5396 (2000).
  • Arbour NC, Lorenz E, Schutte BC et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet. 25(2), 187–191 (2000).
  • Ku CL, von Bernuth H, Picard C et al. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. J. Exp. Med. 204(10), 2407–2422 (2007).
  • Willet KE, Jobe AH, Ikegami M, Newnham J, Brennan S, Sly PD. Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs. Pediatr. Res. 48(6), 782–788 (2000).
  • Hillman NH, Moss TJ, Nitsos I et al. Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatr. Res. 63(4), 388–393 (2008).
  • Petrikin JE, Gaedigk R, Leeder JS, Truog WE. Selective Toll--like receptor expression in human fetal lung. Pediatr. Res. 68(4), 335–338 (2010).
  • Forster-Waldl E, Sadeghi K, Tamandl D et al. Monocyte toll-like receptor 4 expression and LPS-induced cytokine production increase during gestational aging. Pediatr. Res. 58(1), 121–124 (2005).
  • Kollmann TR, Levy O, Montgomery RR, Goriely S. Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity 37(5), 771–783 (2012).
  • Thornton NL, Cody MJ, Yost CC. Toll-like receptor 1/2 stimulation induces elevated interleukin-8 secretion in polymorphonuclear leukocytes isolated from preterm and term newborn infants. Neonatology 101(2), 140–146 (2012).
  • Al-Hertani W, Yan SR, Byers DM, Bortolussi R. Human newborn polymorphonuclear neutrophils exhibit decreased levels of MyD88 and attenuated p38 phosphorylation in response to lipopolysaccharide. Clin. Invest. Med. 30(2), E44–E53 (2007).
  • Dasari P, Zola H, Nicholson IC. Expression of Toll-like receptors by neonatal leukocytes. Pediatr. Allergy. Immunol. 22(2), 221–228 (2011).
  • Tulic MK, Hodder M, Forsberg A et al. Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny. J. Allergy Clin. Immunol. 127(2), 470–478 e1 (2011).
  • Bonner S, Yan SR, Byers DM, Bortolussi R. Activation of extracellular signal-related protein kinases 1 and 2 of the mitogen-activated protein kinase family by lipopolysaccharide requires plasma in neutrophils from adults and newborns. Infect. Immun. 69(5), 3143–3149 (2001).
  • Nathe KE, Mancuso CJ, Parad R et al. Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation. Pediatr. Res. 72(2), 203–211 (2012).
  • Viemann D, Dubbel G, Schleifenbaum S, Harms E, Sorg C, Roth J. Expression of toll-like receptors in neonatal sepsis. Pediatr. Res. 58(4), 654–659 (2005).
  • Yan SR, Qing G, Byers DM, Stadnyk AW, Al-Hertani W, Bortolussi R. Role of MyD88 in diminished tumor necrosis factor alpha production by newborn mononuclear cells in response to lipopolysaccharide. Infect. Immun. 72(3), 1223–1229 (2004).
  • Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG. Development of allergen-specific T-cell memory in atopic and normal children. Lancet 353(9148), 196–200 (1999).
  • Reece P, Thanendran A, Crawford L et al. Maternal allergy modulates cord blood hematopoietic progenitor Toll-like receptor expression and function. J. Allergy Clin. Immunol. 127(2), 447–453 (2011).
  • Williams DL, Ha T, Li C et al. Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality. Crit. Care Med. 31(6), 1808–1818 (2003).
  • Marsik C, Mayr F, Cardona F, Derhaschnig U, Wagner OF, Jilma B. Endotoxaemia modulates Toll-like receptors on leucocytes in humans. Br. J. Haematol. 121(4), 653–656 (2003).
  • Armstrong L, Medford AR, Hunter KJ, Uppington KM, Millar AB. Differential expression of Toll-like receptor (TLR)-2 and TLR-4 on monocytes in human sepsis. Clin. Exp. Immunol. 136(2), 312–319 (2004).
  • Zhang JP, Yang Y, Levy O, Chen C. Human neonatal peripheral blood leukocytes demonstrate pathogen-specific coordinate expression of TLR2, TLR4/MD2, and MyD88 during bacterial infection in vivo. Pediatr. Res. 68(6), 479–483 (2010).
  • Yerkovich ST, Wikstrom ME, Suriyaarachchi D, Prescott SL, Upham JW, Holt PG. Postnatal development of monocyte cytokine responses to bacterial lipopolysaccharide. Pediatr. Res. 62(5), 547–552 (2007).
  • Henneke P, Osmers I, Bauer K, Lamping N, Versmold HT, Schumann RR. Impaired CD14-dependent and independent response of polymorphonuclear leukocytes in preterm infants. J. Perinat. Med. 31(2), 176–183 (2003).
  • Levy O, Coughlin M, Cronstein BN, Roy RM, Desai A, Wessels MR. The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn. J. Immunol. 177(3), 1956–1966 (2006).
  • Caron JE, La Pine TR, Augustine NH, Martins TB, Hill HR. Multiplex analysis of toll-like receptor-stimulated neonatal cytokine response. Neonatology 97(3), 266–273 (2010).
  • Kollmann TR, Crabtree J, Rein-Weston A et al. Neonatal innate TLR-mediated responses are distinct from those of adults. J. Immunol. 183(11), 7150–7160 (2009).
  • Wynn JL, Scumpia PO, Delano MJ et al. Increased mortality and altered immunity in neonatal sepsis produced by generalized peritonitis. Shock 28(6), 675–683 (2007).
  • Wynn JL, Scumpia PO, Winfield RD et al. Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists. Blood 112(5), 1750–1758 (2008).
  • Azizia M, Lloyd J, Allen M, Klein N, Peebles D. Immune status in very preterm neonates. Pediatrics 129(4), e967–e974 (2012).
  • Lisciandro JG, Prescott SL, Nadal-Sims MG et al. Ontogeny of Toll-like and NOD-like receptor-mediated innate immune responses in Papua New Guinean infants. PLoS ONE 7(5), e36793 (2012).
  • Levy O, Jean-Jacques RM, Cywes C et al. Critical role of the complement system in group B streptococcus-induced tumor necrosis factor alpha release. Infect. Immun. 71(11), 6344–e6353 (2003).
  • Berner R, Welter P, Brandis M. Cytokine expression of cord and adult blood mononuclear cells in response to Streptococcus agalactiae. Pediatr. Res. 51(3), 304–309 (2002).
  • Dollner H, Vatten L, Linnebo I, Zanussi GF, Laerdal A, Austgulen R. Inflammatory mediators in umbilical plasma from neonates who develop early-onset sepsis. Biol. Neonate 80(1), 41–47 (2001).
  • Lalor MK, Ben-Smith A, Gorak-Stolinska P et al. Population differences in immune responses to Bacille Calmette-Guerin vaccination in infancy. J. Infect. Dis. 199(6), 795–800 (2009).
  • Philbin VJ, Levy O. Developmental biology of the innate immune response: implications for neonatal and infant vaccine development. Pediatr. Res. 65(5 Pt. 2), 98R–105R (2009).
  • Levy O. Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists. J. Endotoxin Res. 11(2), 113–116 (2005).
  • Belderbos ME, Houben ML, van Bleek GM et al. Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study. Pediatr. Allergy Immunol. 23(1), 65–74 (2012).
  • Belderbos ME, Levy O, Stalpers F, Kimpen JL, Meyaard L, Bont L. Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors. PLoS ONE. 7(3), e33419 (2012).
  • Molloy EJ, O’Neill AJ, Doyle BT et al. Effects of heat shock and hypoxia on neonatal neutrophil lipopolysaccharide responses: altered apoptosis, Toll-like receptor-4 and CD11b expression compared with adults. Biol. Neonate 90(1), 34–39 (2006).
  • Speer CP, Gahr M, Wieland M, Eber S. Phagocytosis-associated functions in neonatal monocyte-derived macrophages. Pediatr. Res. 24(2), 213–216 (1988).
  • Zentay Z, Sharaf M, Qadir M, Drafta D, Davidson D. Mechanism for dexamethasone inhibition of neutrophil migration upon exposure to lipopolysaccharide in vitro: role of neutrophil interleukin-8 release. Pediatr. Res. 46(4), 406–410 (1999).
  • Contrino J, Krause PJ, Slover N, Kreutzer D. Elevated interleukin-1 expression in human neonatal neutrophils. Pediatr. Res. 34(3), 249–252 (1993).
  • May M, Marx A, Seidenspinner S, Speer CP. Apoptosis and proliferation in lungs of human fetuses exposed to chorioamnionitis. Histopathology 45(3), 283–290 (2004).
  • Henning LN, Azad AK, Parsa KV, Crowther JE, Tridandapani S, Schlesinger LS. Pulmonary surfactant protein A regulates TLR expression and activity in human macrophages. J. Immunol. 180(12), 7847–7858 (2008).
  • Bersani I, Kunzmann S, Speer CP. Immunomodulatory properties of surfactant preparations. Expert Rev. Anti Infect. Ther. 11(1), 99–110 (2013).
  • Bersani I, Speer CP, Kunzmann S. Surfactant proteins A and D in pulmonary diseases of preterm infants. Expert Rev. Anti Infect. Ther. 10(5), 573–584 (2012).
  • Fan H, Cook JA. Molecular mechanisms of endotoxin tolerance. J. Endotoxin Res. 10(2), 71–84 (2004).
  • Kallapur SG, Jobe AH, Ball MK et al. Pulmonary and systemic endotoxin tolerance in preterm fetal sheep exposed to chorioamnionitis. J. Immunol. 179(12), 8491–8499 (2007).
  • Kramer BW, Ikegami M, Moss TJ, Nitsos I, Newnham JP, Jobe AH. Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep. Am. J. Respir. Crit. Care Med. 171(1), 73–77 (2005).
  • Claud EC, Lu L, Anton PM, Savidge T, Walker WA, Cherayil BJ. Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. Proc. Natl Acad. Sci. USA 101(19), 7404–7408 (2004).
  • Leaphart CL, Cavallo J, Gribar SC et al. A critical role for TLR4 in the pathogenesis of necrotizing enterocolitis by modulating intestinal injury and repair. J. Immunol. 179(7), 4808–4820 (2007).
  • Chan KL, Wong KF, Luk JM. Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: pathogenesis and therapeutic implications. World J. Gastroenterol. 15(38), 4745–4752 (2009).
  • Wang J, Ford HR, Grishin AV. NF-kappaB-mediated expression of MAPK phosphatase-1 is an early step in desensitization to TLR ligands in enterocytes. Mucosal Immunol. 3(5), 523–534 (2010).
  • Sodhi CP, Shi XH, Richardson WM et al. Toll-like receptor-4 inhibits enterocyte proliferation via impaired beta-catenin signaling in necrotizing enterocolitis. Gastroenterology 138(1), 185–196 (2010).
  • De Wit D, Olislagers V, Goriely S et al. Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns. Blood 103(3), 1030–1032 (2004).
  • Kotiranta-Ainamo A, Apajasalo M, Pohjavuori M, Rautonen N, Rautonen J. Mononuclear cell subpopulations in preterm and full-term neonates: independent effects of gestational age, neonatal infection, maternal pre-eclampsia, maternal betamethason therapy, and mode of delivery. Clin. Exp. Immunol. 115(2), 309–314 (1999).
  • Landmann R, Knopf HP, Link S, Sansano S, Schumann R, Zimmerli W. Human monocyte CD14 is upregulated by lipopolysaccharide. Infect. Immun. 64(5), 1762–1769 (1996).
  • Bhakdi S, Klonisch T, Nuber P, Fischer W. Stimulation of monokine production by lipoteichoic acids. Infect. Immun. 59(12), 4614–4620 (1991).
  • Polin RA, Committee on F, Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 129(5), 1006–1015 (2012).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.