De Gaetano Giuseppe Valerio, Lentini Germana, Coppolino Francesco, Famà Agata, Pietrocola Giampiero, Beninati Concetta
Department of Human Pathology, University of Messina, Messina, Italy.
Department of Biomedical, Dental and Imaging Sciences, University of Messina, Messina, Italy.
Front Microbiol. 2024 Mar 6;15:1367898. doi: 10.3389/fmicb.2024.1367898. eCollection 2024.
The gut represents an important site of colonization of the commensal bacterium (group B Streptococcus or GBS), which can also behave as a deadly pathogen in neonates and adults. Invasion of the intestinal epithelial barrier is likely a crucial step in the pathogenesis of neonatal infections caused by GBS belonging to clonal complex 17 (CC17). We have previously shown that the prototypical CC17 BM110 strain invades polarized enterocyte-like cells through their lateral surfaces using an endocytic pathway. By analyzing the cellular distribution of putative GBS receptors in human enterocyte-like Caco-2 cells, we find here that the alpha 3 (α) and alpha 2 (α) integrin subunits are selectively expressed on lateral enterocyte surfaces at equatorial and parabasal levels along the vertical axis of polarized cells, in an area corresponding to GBS entry sites. The αβ and αβ integrins were not readily accessible in fully differentiated Caco-2 monolayers but could be exposed to specific antibodies after weakening of intercellular junctions in calcium-free media. Under these conditions, anti-αβ and anti-αβ antibodies significantly reduced GBS adhesion to and invasion of enterocytes. After endocytosis, αβ and αβ integrins localized to areas of actin remodeling around GBS containing vacuoles. Taken together, these data indicate that GBS can invade enterocytes by binding to αβ and αβ integrins on the lateral membrane of polarized enterocytes, resulting in cytoskeletal remodeling and bacterial internalization. Blocking integrins might represent a viable strategy to prevent GBS invasion of gut epithelial tissues.
肠道是共生细菌（B族链球菌或GBS）的重要定植部位，而这种细菌在新生儿和成人中也可能表现为致命病原体。肠道上皮屏障的入侵可能是由克隆复合体17（CC17）的GBS引起的新生儿感染发病机制中的关键步骤。我们之前已经表明，典型的CC17 BM110菌株通过内吞途径从其侧面侵入极化的肠上皮样细胞。通过分析人肠上皮样Caco-2细胞中假定的GBS受体的细胞分布，我们在此发现α3（α）和α2（α）整合素亚基在极化细胞垂直轴上赤道和基底旁水平的肠上皮细胞侧面选择性表达，该区域与GBS进入位点相对应。在完全分化的Caco-2单层细胞中，αβ和αβ整合素不易接近，但在无钙培养基中细胞间连接减弱后可暴露于特异性抗体。在这些条件下，抗αβ和抗αβ抗体显著降低了GBS对肠上皮细胞的粘附和侵袭。内吞后，αβ和αβ整合素定位于含GBS液泡周围肌动蛋白重塑区域。综上所述，这些数据表明GBS可通过与极化肠上皮细胞侧膜上的αβ和αβ整合素结合来侵入肠上皮细胞，从而导致细胞骨架重塑和细菌内化。阻断整合素可能是预防GBS侵袭肠道上皮组织的可行策略。
