Pathogenesis of Herpes Stromal Keratitis: Immune Inflammatory Response Mediated by Inflammatory Regulators

Li Wang, Runbiao Wang, Chuyang Xu, Hongyan Zhou, Li Wang, Runbiao Wang, Chuyang Xu, Hongyan Zhou

Abstract

Herpes stromal keratitis (HSK) is one of the primary diseases that cause vision loss or even blindness after herpes simplex virus (HSV)-1 infection. HSK-associated vision impairment is predominantly due to corneal scarring and neovascularization caused by inflammation. In the infected cornea, HSV can activate innate and adaptive immune responses of host cells, which triggers a cascade of reactions that leads to the release of inflammatory cytokines, chemokines, microRNA, and other regulatory factors that have stimulating or inhibitory effects on tissue. Physiologically, host cells show homeostasis. In this review, we summarize the factors involved in HSK pathogenesis from the perspective of immunity, molecules, and pathological angiogenesis. We also describe in detail the pathogenesis of chronic inflammatory lesions of the corneal stroma in response to HSV-1 infection.

Keywords: herpes simplex virus (HSV-1); immune response; inflammation; pathogenesis; stromal keratitis.

Copyright © 2020 Wang, Wang, Xu and Zhou.

Figures

Figure 1
Figure 1
Innate and adaptive immune response in herpes stromal keratitis (HSK) in response to herpes simplex virus (HSV-1) infection. The combination of gD and its receptors [e.g., herpesvirus entry mediator (HVEM), 3-OS-HS, and nectin-1] facilitates virus fusion. HSV-1 and virus analogs [e.g., ploy(I:C), LPS] bind to Toll-like receptors (TLRs) to promote intracellular signaling. Major histocompatibility complex II (MHC-II) transmits the antigenic information on the surface of antigen-presenting cells (APCs) [e.g., dendritic cells (DC), macrophage] to T cells, and activated T cells promote the release of inflammatory factors and neutrophils. The combination of substance P (SP) and the neurokinin-1 receptor (NK1R) activates nuclear factor κB (NF-κB) to increase inflammatory cytokine and chemokine levels.
Figure 2
Figure 2
Regulation of HSK by HVEM. HVEM can interact with immunoglobulin ligands [CD160, B, and T lymphocyte attenuator (BTLA)] and the tumor necrosis factor (TNF) ligand [LIGHT]. Binding of HVEM to LIGHT activates CD4+ T cells. Conversely, the interactions of CD160 and BTLA with HVEM inhibit CD4+ T cell expression. Besides, HVEM can promote the establishment of HSV-1 latency.

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