Förster-Waldl Elisabeth, Sadeghi Kambis, Tamandl Dietmar, Gerhold Bernadette, Hallwirth Ulrike, Rohrmeister Klaudia, Hayde Michael, Prusa Andrea R, Herkner Kurt, Boltz-Nitulescu George, Pollak Arnold, Spittler Andreas
Department of Pediatrics and Juvenile Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Pediatr Res. 2005 Jul;58(1):121-4. doi: 10.1203/01.PDR.0000163397.53466.0F. Epub 2005 May 5.
Premature newborns are highly susceptible to severe bacterial infections. This is partially due to their immature innate immune system, characterized by decreased neutrophil and monocyte activity as well as by reduced concentrations of complement factors. However, additional mechanisms might be important for innate immunity and are still the subject of considerable debate. The importance of pattern recognition domains such as Toll-like receptors (TLR) has been fully acknowledged within the last few years. Therefore, we investigated age-related monocyte TLR4 expression and lipopolysaccharide-induced cytokine secretion from very low birth weight infants (VLBWI) and from newborns after wk 30 of gestation in comparison to healthy adults. In VLBWI, expression of TLR4 surface protein, detected by flow cytometry, and TLR4-specific mRNA, quantified by real time-PCR, were significantly reduced in comparison to mature infants and to adults. Reduced TLR4 expression was paralleled by significantly diminished ex vivo LPS stimulated IL-1beta, IL-6, and tumor necrosis factor-alpha secretion into whole blood. We conclude that, in VLBWI, the minimized expression of TLR4 contributes to the susceptibility of VLBWI to infections with Gram-negative bacteria due to the lack of cytokines to boost initial immune response.
早产儿极易受到严重细菌感染。这部分是由于他们未成熟的先天免疫系统，其特征是中性粒细胞和单核细胞活性降低以及补体因子浓度降低。然而，其他机制可能对先天免疫很重要，并且仍然是相当多争论的主题。在过去几年中，诸如Toll样受体（TLR）等模式识别域的重要性已得到充分认可。因此，我们研究了极低出生体重儿（VLBWI）和妊娠30周后的新生儿与健康成人相比，与年龄相关的单核细胞TLR4表达和脂多糖诱导的细胞因子分泌。在VLBWI中，通过流式细胞术检测到的TLR4表面蛋白表达以及通过实时PCR定量的TLR4特异性mRNA与成熟婴儿和成人相比显著降低。TLR4表达降低与体外LPS刺激的IL-1β、IL-6和肿瘤坏死因子-α分泌到全血中的显著减少同时发生。我们得出结论，在VLBWI中，TLR4表达的最小化导致VLBWI对革兰氏阴性菌感染的易感性，因为缺乏细胞因子来增强初始免疫反应。
