首页> 外文期刊>Infection and immunity >Nontypeable Haemophilus influenzae Adheres to Intercellular Adhesion Molecule 1 (ICAM-1) on Respiratory Epithelial Cells and Upregulates ICAM-1 Expression
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Nontypeable Haemophilus influenzae Adheres to Intercellular Adhesion Molecule 1 (ICAM-1) on Respiratory Epithelial Cells and Upregulates ICAM-1 Expression

机译:非分型流感嗜血杆菌在呼吸道上皮细胞上粘附细胞间粘附分子1(ICAM-1),并上调ICAM-1表达

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Nontypeable Haemophilus influenzae (NTHI) is an important respiratory pathogen. NTHI initiates infection by adhering to the airway epithelium. Here, we report that NTHI interacts with intracellular adhesion molecule 1 (ICAM-1) expressed by respiratory epithelial cells. A fourfold-higher number of NTHI bacteria adhered to Chinese hamster ovary (CHO) cells transfected with human ICAM-1 (CHO-ICAM-1) than to control CHO cells (P ≤ 0.005). Blocking cell surface ICAM-1 with specific antibody reduced the adhesion of NTHI to A549 respiratory epithelial cells by 37% (P = 0.001) and to CHO-ICAM-1 cells by 69% (P = 0.005). Preincubating the bacteria with recombinant ICAM-1 reduced adhesion by 69% (P = 0.003). The adherence to CHO-ICAM-1 cells of NTHI strains deficient in the adhesins P5, P2, HMW1/2, and Hap or expressing a truncated lipooligosaccharide was compared to that of parental strains. Only strain 1128f?, which lacks the outer membrane protein (OMP) P5-homologous adhesin (P5 fimbriae), adhered less well than its parental strain. The numbers of NTHI cells adhering to CHO-ICAM-1 cells were reduced by 67% (P = 0.009) following preincubation with anti-P5 antisera. Furthermore, recombinant ICAM bound to an OMP preparation from strain 1128f+, which expresses P5, but not to that from its P5-deficient mutant, confirming a specific interaction between ICAM-1 and P5 fimbriae. Incubation of respiratory epithelial cells with NTHI increased ICAM-1 expression fourfold (P = 0.001). Adhesion of NTHI to the respiratory epithelium, therefore, upregulates the expression of its own receptor. Blocking interactions between NTHI P5 fimbriae and ICAM-1 may reduce respiratory colonization by NTHI and limit the frequency and severity of NTHI infection.
机译:不可分类的流感嗜血杆菌(NTHI)是一种重要的呼吸道病原体。 NTHI通过粘附在气道上皮上引发感染。在这里,我们报告NTHI与呼吸道上皮细胞表达的细胞内粘附分子1(ICAM-1)相互作用。 NTHI细菌粘附在转染了人ICAM-1(CHO-ICAM-1)的中国仓鼠卵巢(CHO)细胞上的数量是对照CHO细胞的四倍以上( P ≤0.005)。用特异性抗体阻断细胞表面ICAM-1可使NTHI与A549呼吸道上皮细胞的粘附减少37%( P = 0.001),而与CHO-ICAM-1细胞的粘附减少69%( P = 0.005)。用重组ICAM-1对细菌进行预温育可使粘附力降低69%( P = 0.003)。将粘附素P5,P2,HMW1 / 2和Hap缺失或表达截短的脂寡糖的NTHI菌株对CHO-ICAM-1细胞的粘附性与亲本菌株进行了比较。只有缺少外膜蛋白(OMP)P5同源黏附素(P5菌毛)的1128f ?菌株比其亲本菌株粘附得差。与抗P5抗血清预孵育后,粘附到CHO-ICAM-1细胞的NTHI细胞数量减少了67%( P = 0.009)。此外,重组ICAM与表达P5的菌株1128f + 的OMP制剂结合,但不与其P5缺陷型突变体的OMP制剂结合,证实了ICAM-1和P5菌毛之间的特异性相互作用。用NTHI孵育呼吸道上皮细胞可使ICAM-1表达增加四倍( P = 0.001)。因此,NTHI对呼吸道上皮的粘附会上调其自身受体的表达。阻断NTHI P5菌毛和ICAM-1之间的相互作用可能会减少NTHI引起的呼吸道定植,并限制NTHI感染的频率和严重程度。

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