Chemokine CXCL10 and Coronavirus-Induced Neurologic Disease

Viral Immunol. Jan/Feb 2019;32(1):25-37. doi: 10.1089/vim.2018.0073. Epub 2018 Aug 15.

Abstract

Chemokines (chemotactic cytokines) are involved in a wide variety of biological processes. Following microbial infection, there is often robust chemokine signaling elicited from infected cells, which contributes to both innate and adaptive immune responses that control growth of the invading pathogen. Infection of the central nervous system (CNS) by the neuroadapted John Howard Mueller (JHM) strain of mouse hepatitis virus (JHMV) provides an excellent example of how chemokines aid in host defense as well as contribute to disease. Intracranial inoculation of the CNS of susceptible mice with JHMV results in an acute encephalomyelitis characterized by widespread dissemination of virus throughout the parenchyma. Virus-specific T cells are recruited to the CNS, and control viral replication through release of antiviral cytokines and cytolytic activity. Sterile immunity is not acquired, and virus will persist primarily in white matter tracts leading to chronic neuroinflammation and demyelination. Chemokines are expressed and contribute to defense as well as chronic disease by attracting targeted populations of leukocytes to the CNS. The T cell chemoattractant chemokine CXCL10 (interferon-inducible protein 10 kDa, IP-10) is prominently expressed in both stages of disease, and serves to attract activated T and B lymphocytes expressing CXC chemokine receptor 3 (CXCR3), the receptor for CXCL10. Functional studies that have blocked expression of either CXCL10 or CXCR3 illuminate the important role of this signaling pathway in host defense and neurodegeneration in a model of viral-induced neurologic disease.

Keywords: CNS infection; CXCL10; coronavirus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Central Nervous System Viral Diseases / immunology*
  • Central Nervous System Viral Diseases / pathology
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology*
  • Chemotactic Factors
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology
  • Demyelinating Diseases / immunology*
  • Demyelinating Diseases / virology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Murine hepatitis virus / immunology*
  • Murine hepatitis virus / pathogenicity
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Signal Transduction
  • T-Lymphocytes / immunology

Substances

  • Chemokine CXCL10
  • Chemotactic Factors
  • Cxcr3 protein, mouse
  • Receptors, CXCR3