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Invited Review

Innate immunity in human newborn infants: prematurity means more than immaturity

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Pages 25-31 | Received 23 Aug 2009, Accepted 29 Mar 2010, Published online: 23 Jun 2010

References

  • Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, et al Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002;110:285–291.
  • Stoll BJ, Hansen N. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin Perinatol 2003;27:293–301.
  • Laws PJ, Grayson N, Sullivan EA. Australia's mothers and babies 2004. Perinatal statistics series no. 18. AIHW cat. no. PER 34. Sydney: AIHW National Perinatal Statistics Unit; 2006.
  • Barton L, Hodgman JE, Pavlova Z. Causes of death in the extremely low birth weight infant. Pediatrics 1999;103:446–451.
  • Payne NR, Carpenter JH, Badger GJ, Horbar JD, Rogowski J. Marginal increase in cost and excess length of stay associated with nosocomial bloodstream infections in surviving very low birth weight infants. Pediatrics 2004;114:348–355.
  • Keyworth N, Millar MR, Holland KT. Development of cutaneous microflora in premature neonates. Arch Dis Child 1992;67:797–801.
  • Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age. Nat Rev Immunol 2004;4:553–564.
  • Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol 2007;7:379–390.
  • Mittendorf R, Roizen N, Moawad A, Khoshnood B, Lee KS. Association between cerebral palsy and coagulase-negative staphylococci. Lancet 1999;354:1875–1876.
  • Gonzalez A, Sosenko IR, Chandar J, Hummler H, Claure N, Bancalari E. Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less. J Pediatr 1996;128:470–478.
  • Bassler D, Stoll BJ, Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS. Using a count of neonatal morbidities to predict poor outcome in extremely low birth weight infants: added role of neonatal infection. Pediatrics 2009;123:313–318.
  • Shah DK, Doyle LW, Anderson PJ, Bear M, Daley AJ, Hunt RW, Inder TE. Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormalities on magnetic resonance imaging at term. J Pediatr 2008;153:170–175.
  • Kiechl-Kohlendorfer U, Ralser E, Pupp Peglow U, Reiter G, Trawoger R. Adverse neurodevelopmental outcome in preterm infants: risk factor profiles for different gestational ages. Acta Paediatr 2009;98:792–796.
  • Stoll BJ. Infections of the neonatal infant. In: Kliegmann RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson textbook of pediatrics. 18th ed. Philadelphia: Elsevier Saunders; 2007. pp 794–811.
  • Fanaroff AA, Korones SB, Wright LL, Verter J, Poland RL, Bauer CR, Tyson JE, Philips JB, 3rd, Edwards W, Lucey JF, et al Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network. Pediatr Infect Dis J 1998;17:593–598.
  • Fleer A, Gerards LJ, Aerts P, Westerdaal NA, Senders RC, vanDijk H, Verhoef J. Opsonic defense to Staphylococcus epidermidis in the premature neonate. J Infect Dis 1985;152:930–937.
  • Krediet TG, Beurskens FJ, van Dijk H, Gerards LJ, Fleer A. Antibody responses and opsonic activity in sera of preterm neonates with coagulase-negative staphylococcal septicemia and the effect of the administration of fresh frozen plasma. Pediatr Res 1998;43:645–651.
  • Notarangelo LD, Chirico G, Chiara A, Colombo A, Rondini G, Plebani A, Martini A, Ugazio AG. Activity of classical and alternative pathways of complement in preterm and small for gestational age infants. Pediatr Res 1984;18:281–285.
  • Lin FY, Philips JB, 3rd, Azimi PH, Weisman LE, Clark P, Rhoads GG, Regan J, Concepcion NF, Frasch CE, Troendle J, et al Level of maternal antibody required to protect neonates against early- onset disease caused by group B Streptococcus type Ia: a multicenter, seroepidemiology study. J Infect Dis 2001;184:1022–1028.
  • Lin FY, Weisman LE, Azimi PH, Philips JB 3rd, Clark P, Regan J, Rhoads GG, Frasch CE, Gray BM, Troendle J, et al Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen. J Infect Dis 2004;190:928–934.
  • DeJonge M, Burchfield D, Bloom B, Duenas M, Walker W, Polak M, Jung E, Millard D, Schelonka R, Eyal F, et al Clinical trial of safety and efficacy of INH-A21 for the prevention of nosocomial staphylococcal bloodstream infection in premature infants. J Pediatr 2007;151:260–265.
  • Benjamin DK Jr, Schelonka R, White R, Holley HP Jr, Bifano E, Cummings J, Adcock K, Kaufman D, Puppala B, Riedel P, et al A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin. J Perinatol 2006;26:290–295.
  • Levy O. Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes. J Leukoc Biol 2004;76:909–925.
  • Strunk T, Doherty D, Richmond P, Simmer K, Charles A, Levy O, Liyanage K, Smith T, Currie A, Burgner D. Reduced levels of antimicrobial proteins and peptides in human cord blood plasma. Arch Dis Child Fetal Neonatal Ed 2009;94:F230–F231.
  • Schaller-Bals S, Schulze A, Bals R. Increased levels of antimicrobial peptides in tracheal aspirates of newborn infants during infection. Am J Respir Crit Care Med 2002;165:992–995.
  • Starner TD, Agerberth B, Gudmundsson GH, McCray PB Jr. Expression and activity of {beta}-defensins and LL-37 in the developing human lung. J Immunol 2005;174:1608–1615.
  • Marchini G, Lindow S, Brismar H, Stabi B, Berggren V, Ulfgren AK, Lonne-Rahm S, Agerberth B, Gudmundsson GH. The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa. Br J Dermatol 2002;147:1127–1134.
  • Kai-Larsen Y, Bergsson G, Gudmundsson GH, Printz G, Jornvall H, Marchini G, Agerberth B. Antimicrobial components of the neonatal gut affected upon colonization. Pediatr Res 2007;61:530–536.
  • Turner MW. Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol Today 1996;17:532–540.
  • Ip WK, Takahashi K, Moore KJ, Stuart LM, Ezekowitz RA. Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome. J Exp Med 2008;205:169–181.
  • Dahl M, Tybjaerg-Hansen A, Schnohr P, Nordestgaard BG. A population-based study of morbidity and mortality in mannose-binding lectin deficiency. J Exp Med 2004;199:1391–1399.
  • Sutherland AM, Walley KR, Russell JA. Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults. Crit Care Med 2005;33:638–644.
  • Garred P, J Strom, Quist L, Taaning E, Madsen HO. Association of mannose-binding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome. J Infect Dis 2003;188:1394–1403.
  • Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 2003;37:1496–1505.
  • Bodamer OA, Mitterer G, Maurer W, Pollak A, Mueller MW, Schmidt WM. Evidence for an association between mannose-binding lectin 2 (MBL2) gene polymorphisms and pre-term birth. Genet Med 2006;8:518–524.
  • Dzwonek AB, Neth OW, Thiebaut R, Gulczynska E, Chilton M, Hellwig T, Bajaj-Elliott M, Hawdon J, Klein NJ. The role of mannose-binding lectin in susceptibility to infection in preterm neonates. Pediatr Res 2008;63:680–685.
  • Frakking FN, Brouwer N, Zweers D, Merkus MP, Kuijpers TW, Offringa M, Dolman KM. High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates. Clin Exp Immunol 2006;145:5–12.
  • Frakking FN, Brouwer N, van Eijkelenburg NK, Merkus MP, Kuijpers TW, Offringa M, Dolman KM. Low mannose-binding lectin (MBL) levels in neonates with pneumonia and sepsis. Clin Exp Immunol 2007;150:255–262.
  • Dean MM, Minchinton RM, Heatley S, Eisen DP. Mannose binding lectin acute phase activity in patients with severe infection. J Clin Immunol 2005;25:346–352.
  • Gessler P, Luders R, Konig S, Haas N, Lasch P, Kachel W. Neonatal neutropenia in low birthweight premature infants. Am J Perinatol 1995;12:34–38.
  • Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 1989;321:557–562.
  • Carr R. Neutrophil production and function in newborn infants. Br J Haematol 2000;110:18–28.
  • Falconer AE, Carr R, Edwards SW. Impaired neutrophil phagocytosis in preterm neonates: lack of correlation with expression of immunoglobulin or complement receptors. Biol Neonate 1995;68:264–269.
  • Kallman J, Schollin J, Schalen C, Erlandsson A, Kihlstrom E. Impaired phagocytosis and opsonisation towards group B streptococci in preterm neonates. Arch Dis Child Fetal Neonatal Ed 1998;78:F46–F50.
  • Peden DB, VanDyke K, Ardekani A, Mullett MD, Myerberg DZ, VanDyke C. Diminished chemiluminescent responses of polymorphonuclear leukocytes in severely and moderately preterm neonates. J Pediatr 1987;111:904–906.
  • Driscoll MS, Thomas VL, Ramamurthy RS, Casto DT. Longitudinal evaluation of polymorphonuclear leukocyte chemiluminescence in premature infants. J Pediatr 1990;116:429–434.
  • Ambruso DR, Stork LC, Gibson BE, Thurman GW. Increased activity of the respiratory burst in cord blood neutrophils: kinetics of the NADPH oxidase enzyme system in subcellular fractions. Pediatr Res 1987;21:205–210.
  • Yamazaki M, Matsuoka T, Yasui K, Komiyama A, Akabane T. Increased production of superoxide anion by neonatal polymorphonuclear leukocytes stimulated with a chemotactic peptide. Am J Hematol 1988;27:169–173.
  • Yost CC, Cody MJ, Harris ES, Thornton NL, McInturff AM, Martinez ML, Chandler NB, Rodesch CK, Albertine KH, Petti CA, et al Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood 2009;113:6419–6427.
  • Carr R, Brocklehurst P, Dore CJ, Modi N. Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial. Lancet 2009;373:226–233.
  • Carr R, Modi N, Dore C. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev 2003; CD003066.
  • Ahmad M, Fleit HB, Golightly MG, La Gamma EF. In vivo effect of recombinant human granulocyte colony-stimulating factor on phagocytic function and oxidative burst activity in septic neutropenic neonates. Biol Neonate 2004;86:48–54.
  • Christian Gille BSLTCFPTO. A new method to quantify phagocytosis and intracellular degradation using green fluorescent protein-labeled Escherichia coli: comparison of cord blood macrophages and peripheral blood macrophages of healthy adults. Cytometry Part A 2006;69A:152–154.
  • Hallwirth U, Pomberger G, Pollak A, Roth E, Spittler A. Monocyte switch in neonates: high phagocytic capacity and low HLA-DR expression in VLBWI are inverted during gestational aging. Pediatr Allergy Immunol 2004;15:513–516.
  • Jones CA, Holloway JA, Warner JO. Phenotype of fetal monocytes and B lymphocytes during the third trimester of pregnancy. J Reprod Immunol 2002;56:45–60.
  • Holloway JA, Thornton CA, Diaper ND, Howe DT, Warner JO. Phenotypic analysis of circulating dendritic cells during the second half of human gestation. Pediatr Allergy Immunol 2009;20:119–125.
  • Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783–801.
  • Kawai T, Akira S. Toll-like receptor and RIG-I-like receptor signaling. Ann N Y Acad Sci 2008;1143:1–20.
  • 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 2001;49:589–593.
  • 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 2004;173:4627–4634.
  • Viemann D, Dubbel G, Schleifenbaum S, Harms E, Sorg C, Roth J. Expression of toll-like receptors in neonatal sepsis. Pediatr Res 2005;58:654–659.
  • Forster-Waldl E, Sadeghi K, Tamandl D, Gerhold B, Hallwirth U, Rohrmeister K, Hayde M, Prusa AR, Herkner K, Boltz-Nitulescu G, et al Monocyte toll-like receptor 4 expression and LPS-induced cytokine production increase during gestational aging. Pediatr Res 2005;58:121–124.
  • 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 2006;177:1956–1966.
  • 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 2004;72:1223–1229.
  • Sadeghi K, Berger A, Langgartner M, Prusa AR, Hayde M, Herkner K, Pollak A, Spittler A, Forster-Waldl E. Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling. J Infect Dis 2007;195:296–302.
  • Lorenz E, Hallman M, Marttila R, Haataja R, Schwartz DA. Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish Population. Pediatr Res 2002;52:373–376.
  • Krediet TG, Wiertsema SP, Vossers MJ, Hoeks SB, Fleer A, Ruven HJ, Rijkers GT. Toll-like receptor 2 polymorphism is associated with preterm birth. Pediatr Res 2007;62:474–476.
  • Vitoratos N, Papadias C, Economou E, Makrakis E, Panoulis C, Creatsas G. Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome. Mediators Inflamm 2006;2006:30485.
  • Hartel C, Osthues I, Rupp J, Haase B, Roder K, Gopel W, Herting E, Schultz C. Characterisation of the host inflammatory response to Staphylococcus epidermidis in neonatal whole blood. Arch Dis Child Fetal Neonatal Ed 2008;93:F140–F145.
  • Strunk T, Temming P, Gembruch U, Reiss I, Bucsky P, Schultz C. Differential maturation of the innate immune response in human fetuses. Pediatr Res 2004;56:219–226.
  • Schibler KR, Trautman MS, Liechty KW, White WL, Rothstein G, Christensen RD. Diminished transcription of interleukin-8 by monocytes from preterm neonates. J Leukoc Biol 1993;53:399–403.
  • Yachie A, Takano N, Ohta K, Uehara T, Fujita S, Miyawaki T, Taniguchi N. Defective production of interleukin-6 in very small premature infants in response to bacterial pathogens. Infect Immun 1992;60:749–753.
  • Angelone DF, Wessels MR, Coughlin M, Suter EE, Valentini P, Kalish LA, Levy O. 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 2006;60:205–209.
  • Kenzel S, Mancuso G, Malley R, Teti G, Golenbock DT, Henneke P. c-Jun kinase is a critical signaling molecule in a neonatal model of group B streptococcal sepsis. J Immunol 2006;176:3181–3188.
  • Strunk T, Richmond P, Simmer K, Currie A, Levy O, Burgner D. Neonatal immune responses to coagulase-negative staphylococci. Curr Opin Infect Dis 2007;20:370–375.
  • Karlsson H, Hessle C, Rudin A. Innate immune responses of human neonatal cells to bacteria from the normal gastrointestinal flora. Infect Immun 2002;70:6688–6696.
  • Marodi L. Innate cellular immune responses in newborns. Clin Immunol 2006;118:137–144.
  • Yerkovich ST, Wikstrom ME, Suriyaarachchi D, Prescott SL, Upham JW, Holt PG. Postnatal development of monocyte cytokine responses to bacterial lipopolysaccharide. Pediatr Res 2007;62:547–552.
  • LeBouder E, Rey-Nores JE, Raby AC, Affolter M, Vidal K, Thornton CA, Labeta MO. Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk. J Immunol 2006;176:3742–3752.
  • Bloom B, Schelonka R, Kueser T, Walker W, Jung E, Kaufman D, Kesler K, Roberson D, Patti J, Hetherington S. Multicenter study to assess safety and efficacy of INH-A21, a donor-selected human staphylococcal immunoglobulin, for prevention of nosocomial infections in very low birth weight infants. Pediatr Infect Dis J 2005;24:858–866.
  • Ohlsson A, Lacy JB. Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants. Cochrane Database Syst Rev 2004: CD000361.
  • Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2004: CD001239.
  • Levy O, Martin S, Eichenwald E, Ganz T, Valore E, Carroll SF, Lee K, Goldmann D, Thorne GM. Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein. Pediatrics 1999;104:1327–1333.
  • Levin M, Quint PA, Goldstein B, Barton P, Bradley JS, Shemie SD, Yeh T, Kim SS, Cafaro DP, Scannon PJ, et al Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet 2000;356:961–967.
  • Wynn JL, Scumpia PO, Winfield RD, Delano MJ, Kelly-Scumpia K, Barker T, Ungaro R, Levy O, Moldawer LL. Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists. Blood 2008;112:1750–1758.
  • Philbin VJ, Levy O. Developmental Biology of the Innate Immune Response: Implications for Neonatal and Infant Vaccine Development. Pediatric Res 2009;65:98R–105R.
  • Wille-Reece U, Flynn BJ, Lore K, Koup RA, Miles AP, Saul A, Kedl RM, Mattapallil JJ, Weiss WR, Roederer M, Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J Exp Med 2006;203:1249–1258.
  • Wynn JL, Neu J, Moldawer LL, Levy O. Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis. J Perinatol 2009;29:79–88.
  • Deshpande G, Rao S, Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials. Lancet 2007;369:1614–1620.
  • Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science 2001;292:1115–1118.
  • Marschan E, Kuitunen M, Kukkonen K, Poussa T, Sarnesto A, Haahtela T, Korpela R, Savilahti E, Vaarala O. Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation. Clin Exp Allergy 2008;38:611–618.
  • Bell SG. Immunomodulation, Part V: probiotics. Neonatal Netw 2007;26:57–60.
  • Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Biol Neonate 2002;82:103–108.

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