Figure 1: EC functions associated with homeostasis and resistance to infection.

(A) In steady state EC have mechanisms that act to prevent inflammation through their ability to produce prostaglandin I₂, which together with the constitutive expression of endothelial nitric oxide synthase (eNOS), antagonizes cytokine mediated upregulation of adhesion molecules. Basal expression of tissue factor pathway inhibitors (TFPIs) block the initiation of the coagulation cascade and inhibit platelet adhesion and aggregation. (B) EC contain Weibel–Palade bodies (WPB), which are cytoplasmic storage vesicles that contain von Willebrand factor (vWF) and P-selectin, in response to vascular injury, complement activation via the C1qRs and C5aR, EC release von Willebrand factor that supports the local recruitment of platelets and coagulation to prevent blood loss. EC damage can also promotes expression of adhesion molecules. (C) EC express cytokine receptors (eg IFN-γR and TNFR) and many classes of PRRs (e.g. TLR2, TLR4, TLR9, RIG-1, and STING) relevant to bacterial and viral infection, which allow EC to respond to infection by the activation of NF-κB and MAPK. Further, EC activation by pathogen leads to the up-regulation of adhesion molecules such as ICAM1, VCAM1, Selectins and CX3CL1, and the release of chemokines and pro-inflammatory cytokines such as IL-1/6/8, MCP, and CXCL9/10/11. (D) EC activation by IFN-γ, TNF-α or Type I IFNs induce a number of mechanisms that can restrict the growth of micro-organisms. IFN-γ and TNF-α activate EC to upregulate indoleamine 2,3-dioxygenase (IDO) leading to tryptophan degradation and starvation of T. gondii, S. aureus and Rickettsia. Moreover, EC production of nitric oxide (NO) inhibits microbial growth of Rickettsia and M. tuberculosis. Further, Type I IFNs induced expression of interferon-stimulated genes (ISG) inhibit viral replication during HCMV infection.