[Changes and clinical significance of Toll-like receptor 2 and 4 expression in neonatal infections].
OBJECTIVE
Neonates are vulnerable to various infections because of their immature immune responses. Toll-like receptors could induce immune responses, both the innate and the acquired immune responses. The aim of the present study was to investigate the changes of TLR2 and TLR4 in neonatal infections, and to determine their roles in anti-infection immune reaction.


METHODS
A total of 200 infants were divided into six groups: sepsis group (n = 21), bacterial pneumonia group (n = 70), bacterial meningitis group (n = 17), urinary tract infection group (n = 38), congenital syphilis group (n = 11) and non-infection group (n = 48). The TLR mRNA was determined by RT-PCR. The protein expression of TLR and the percentage of TLR positive cells were evaluated through flow cytometric analysis.


RESULTS
1. The TLR2 mRNA expression increased significantly in the sepsis group (6.14 +/- 0.80), most significantly in the Gram positive sepsis group (6.43 +/- 0.74). TLR2 mRNA expression was also significantly higher in the bacterial pneumonia group (5.49 +/- 0.62), the bacterial meningitis group (5.61 +/- 0.60) and the congenital syphilis group (5.89 +/- 0.38). TLR2 protein expression was the highest in the sepsis group and significantly increased in the bacterial pneumonia group, bacterial meningitis group and the congenital syphilis groups as well, all were higher than the TLR2 protein expression of the non-infectious group (1.27 +/- 0.75). The TLR2 protein expression in the Gram positive bacterial sepsis group was 2.54 +/- 0.68, that of Gram negative bacterial sepsis group was 1.25 +/- 0.51 (P < 0.05). The percentage of TLR2 positive cells in the neonatal infection group was (70.95 +/- 20.15)%, which did not differ significantly from that of non-infection group. 2. The mRNA expression of TLR4 was the highest in the sepsis group (6.20 +/- 1.59), while that in the Gram negative bacterial sepsis group was 6.78 +/- 1.79, higher than that of the Gram positive bacterial sepsis group, 5.39 +/- 0.78, (t = 2.29, P = 0.037). TLR4 mRNA expression increased significantly in the bacterial pneumonia group (5.33 +/- 1.07), the bacterial meningitis group (5.87 +/- 0.70) and the urinary tract infection group (5.38 +/- 0.91). There were no significant differences in TLR4 protein expression among these groups. The percentage of TLR4 positive cells in the neonatal infection groups was (0.71 +/- 0.31)%, higher than that of non- infection group (0.29 +/- 0.36)%. 3. In the Gram positive bacterial sepsis group, the mRNA expression of TLR2 (6.43 +/- 0.74) was higher than the mRNA expression of TLR4 (5.39 +/- 0.78), (t = 1.56, P = 0.024). In the Gram negative bacterial sepsis group, the mRNA expression of TLR4 (6.78 +/- 0.79) was significantly higher than the mRNA expression of TLR2 (5.64 +/- 0.68) (t = 2.63, P = 0.011). In the sepsis group, the TLR2 protein expression was significantly higher than the expression of TLR4 (t = 1.06, P = 0.044). The percentage of TLR4 positive cells was lower than the percentage of TLR2 positive cells among all these groups, P < 0.01. 4. Correlation analysis on gestational age and the mRNA expression, the protein expression and the percentage of TLR2 and TLR4 positive cells among all these groups did not show any statistical significance.


CONCLUSIONS
The mRNA and the protein expression of TLR2 and the mRNA expression of TLR2 increased significantly in the studied neonatal infection groups, especially in the severe sepsis groups. The mRNA expression of TLR2 increased mainly in the Gram positive bacterial infection groups, and the mRNA expression of TLR4 increased in the Gram negative bacterial infection groups, suggesting that both the TLR2 and TLR4 signal pathway took part in the immune mechanism of neonatal infection, providing new idea and experimental basis for further understanding of immune mechanism of neonatal infection.
Zhang
Jin-ping
JP
Department of Neurology, Children's Hospital of Fudan University, The key laboratory of public health ministry, Shanghai 200032, China.
Chen
Chao
C
Yang
Yi
Y
D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D016908:Gram-Positive Bacterial Infections / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D016920:Meningitis, Bacterial / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology; D018805:Sepsis / Q000276:immunology / Q000382:microbiology; D013590:Syphilis, Congenital / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology
C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4