Human neonatal peripheral blood leukocytes demonstrate pathogen-specific coordinate expression of TLR2, TLR4/MD2, and MyD88 during bacterial infection in vivo.
Toll-like receptors (TLRs) play important roles in infection. We have previously reported TLR2 is up-regulated in neonatal Gram-positive (G+) bacteremia, whereas TLR4 is up-regulated in neonatal Gram-negative (G-) bacteremia. For functional signaling, TLR4 requires myeloid differentiation (MD)-2, and both TLR2 and TLR4 signal need myeloid differentiation factor (MyD88). However, it is unknown whether newborns can enhance expression of MD-2 and MyD88 with bacterial infection in coordination with TLR expression. We characterized neonatal peripheral blood leukocyte expression of MD-2 and MyD88 in relation to TLR2/4 in newborns. TLR2 mRNA expression by PBMCs and TLR2 protein expression by monocytes and granulocytes were significantly increased in the G+ bacteremia group. TLR4 mRNA on PMBCs and protein expression on monocytes and granulocytes were significantly increased in the G- bacterial group. Remarkably, although, MyD88 mRNA was increased in all patients with documented bacterial infection and correlated with both TLR2 and TLR4, MD-2 mRNA was selectively increased in G- bacterial group, wherein it correlated with TLR4 but not with TLR2 mRNA. Our findings demonstrate that during bacterial infection in vivo, newborns selectively and coordinately amplify the TLR2-MyD88 pathway in G+ bacterial infection and the TLR4/MD2/MyD88 pathway in G- bacterial infection, suggesting key roles for innate immune pathway in neonatal responses to bacterial infection.
Zhang
Jin-Ping
JP
Division of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, People's Republic of China.
Yang
Yi
Y
Levy
Ofer
O
Chen
Chao
C
D001424:Bacterial Infections / Q000097:blood / Q000276:immunology*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007231:Infant, Newborn / Q000097:blood / Q000276:immunology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology*; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
J Perinatol. 2009 Feb;29(2):79-88
18769381
Mol Immunol. 2008 Jun;45(11):3268-77
18384879
J Infect Dis. 2007 Jan 15;195(2):296-302
17191175
Science. 2008 Aug 1;321(5889):691-6
18669862
Biochem Biophys Res Commun. 2005 Mar 11;328(2):586-90
15694388
Pediatr Res. 2007 Nov;62(5):547-52
17805207
Pediatr Res. 2001 Jan;49(1):81-3
11134496
Immunity. 1999 Jul;11(1):115-22
10435584
Science. 2003 Aug 1;301(5633):640-3
12855817
Pediatr Res. 2005 Oct;58(4):654-9
16189189
Nat Rev Immunol. 2007 May;7(5):379-90
17457344
Curr Opin Immunol. 2006 Feb;18(1):3-9
16343886
J Immunol. 2004 Oct 1;173(7):4627-34
15383597
Zhonghua Er Ke Za Zhi. 2007 Feb;45(2):130-3
17456342
Br J Haematol. 2003 May;121(4):653-6
12752109
Infect Immun. 1995 Jan;63(1):248-52
7528732
Am J Infect Control. 2009 Apr;37(3):201-3
19059676
Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4186-91
15010525
J Perinat Med. 2003;31(2):176-83
12747235
Crit Care Med. 2009 Jan;37(1):132-9
19050613
Infect Immun. 2004 Mar;72(3):1223-9
14977922
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14459-63
10588727
Cytokine. 2010 Mar;49(3):237-44
19264502
Curr Opin Pediatr. 2003 Jun;15(3):278-82
12806257
Microbes Infect. 2002 Jul;4(9):903-14
12106783
J Exp Med. 2003 Oct 6;198(7):1035-42
14517279
Nat Rev Immunol. 2004 Jul;4(7):499-511
15229469
Nat Immunol. 2002 Jul;3(7):667-72
12055629
Nature. 2007 Oct 18;449(7164):819-26
17943118
Blood. 2008 Sep 1;112(5):1750-8
18591384
J Immunol. 2000 Apr 1;164(7):3471-5
10725698
Nature. 1997 Jul 24;388(6640):394-7
9237759
Pediatr Res. 2004 Aug;56(2):219-26
15181184
Science. 1998 Dec 11;282(5396):2085-8
9851930
J Exp Med. 2007 Oct 1;204(10):2407-22
17893200
Pediatr Res. 2005 Jul;58(1):121-4
15879290
Pediatr Res. 2009 Aug;66(2):179-84
19390489