1. Summary of lipid raft-associated signaling pathways involved in Afa/Dr DAEC pathogenesis.
Summary of lipid raft-associated signaling pathways involved in Afa/Dr DAEC pathogenesis. A high-magnification micrograph shows a bacterium interacting with a large number of microvilli at an early time postinfection. Afa/Dr adhesins recognize as receptors the GPI-anchored hDAF, hCEA, and hCEACAM6 and the transmembrane hCEACAM1 proteins. hDAF, hCEA, and hCEACAM6 are endogenously associated with lipid rafts, and a part of hCEACAM1 is translocated within membrane lipid rafts after Afa/Dr DAEC infection. hDAF-dependent signaling involving protein tyrosine kinase(s), phospholipase Cγ, phosphatidylinositol 3-kinase (PI3K), protein kinase C, and an increase in [Ca2+]i leads to structural and functional lesions at the brush border of enterocyte-like cells. hDAF-, hCEA-, and hCEACAM6-dependent signaling involving the Rho GTPase Cdc42 and ERM proteins leads to membrane elongation. hDAF-dependent signaling involving MAPKs and PI3K/Akt lead to HIF-α-dependent VEGF production and epithelial-mesenchymal transition (EMT). hDAF-dependent signaling involving MAPKs leads to proinflammatory cytokines responses, PMNL transmigration, and autophagy followed by cell detachment. Src kinase is necessary for hDAF clustering around adhering bacteria. Phosphorylation of hCEACAM1-4L at ITIMs and recruitment of SHP-2 lead to a negative regulation of phosphorylation of Src associated with hDAF signaling. The DraE-, DaaE-, and AfaE-triggered dynamic microtubule-dependent internalization of bacteria is a lipid raft-dependent phenomenon involving hDAF, hCEACAM1, hCEA, and hCEACAM6.
Alain L. Servin Clin. Microbiol. Rev. 2014; doi: /CMR