CXCR2 Signaling and Host Defense Following Coronavirus-Induced Encephalomyelitis

Abstract

Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the CNS of susceptible strains of mice results in widespread replication within glial cells, accompanied by infiltration of virus-specific T lymphocytes that control the virus through cytokine secretion and cytolytic activity. The virus persists within the white matter tracts of surviving mice, resulting in demyelination that is amplified by inflammatory T cells and macrophages. In response to infection, numerous cytokines/chemokines are secreted by resident cells of the CNS and inflammatory leukocytes that participate in both host defense and disease. Among these are the ELR-positive chemokines that are able to signal through CXC chemokine receptors including CXCR2. Shortly after JHMV infection, ELR-positive chemokines contribute to host defense by attracting CXCR2-expressing cells, including polymorphonuclear cells, to the CNS that aid host defense by increasing the permeability of the blood–brain barrier. During chronic disease, CXCR2 signaling on oligodendroglia protects these cells from apoptosis and restricts the severity of demyelination. This review covers aspects related to host defense and disease in response to JHMV infection and highlights the different roles of CXCR2 signaling in these processes.

Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza Viruses

“…Chemokine receptors such as CXCR2 (IL8RB) are important factors that determine the severity of coronavirus infections. Blocking the expression of these proteins correlates with a bad outcome of the disease and the inability to control virus replication [ 57 ]. Cathepsins of the host cell play an important role in virus infections; one of their functions is to activate virus envelope glycoproteins (e.g., CTSB).…”

ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease

“…Among the chemokines expressed during infection are members of the ELR(+) chemokine family CXCL1 and CXCL2. CXCL1 and CXCL2 are potent chemoattractants for peripheral mononuclear cells (PMNs), binding and signaling through their receptor CXCR2 (Wolpe et al, 1989 ; Moser et al, 1990 ; Schumacher et al, 1992 ; Marro et al, 2012 ; Weinger et al, 2013 ). Moreover, PMNs have been shown to enhance central nervous system (CNS) inflammation by disrupting blood brain barrier (BBB) integrity in animal models of spinal cord injury (SCI; Tonai et al, 2001 ; Gorio et al, 2007 ), autoimmune demyelination (Carlson et al, 2008 ), and JHMV-induced encephalomyelitis (Zhou et al, 2003 ), while blocking or silencing of CXCR2 signaling mutes inflammation and tissue damage in mouse models in which PMN infiltration is critical to disease initiation (Kielian et al, 2001 ; Belperio et al, 2005 ; Londhe et al, 2005a , b ; Strieter et al, 2005 ; Gorio et al, 2007 ; Wareing et al, 2007 ; Carlson et al, 2008 ).…”