Immunopathology in the brain of mice following vertical transmission of Coxsackievirus B4

Type B coxsackieviruses and central nervous system disorders: critical review of reported associations

“…58 In this setting, congenital transmission of CV-B to the CNS triggers immune response marked by an elevation of pro-inflammatory cytokines, chemokines, and inflammatory cell infiltration accompanied by tissue lesions. 50,59 The elevation of cytokine levels because of infection could be pathogenic. Indeed, the sequelae of cytokine induction in the brain can be long lasting and far exceeds the persistence of the initiating factor (the viral infection), thus potentially participating in the development of neurodegenerative diseases such as Parkinson disease.…”

“…It has been reported that CNS infection with CV-B induces proinflammatory cytokine production, infiltration of inflammatory cells through the BBB and gliosis. 86,[120][121][122][123] In some of these studies, CV-B established a persistent infection in the CNS of mice. 86,120 Maladaptive gliosis can result in neurodegeneration.…”

“…129 With respect to CV-B infections in mice, infections at an earlier age (at birth or during foetal life) induce an on-going immune response marked by an elevated secretion of inflammatory cytokines (IL-1β, TNFα, IL-6), gliosis, and immune cell infiltration of brain parenchyma (Figure 3). 86,120 Hence, CV-B infections as an activator of inflammatory cytokines expression might represent an upstream factor in the pathogenic process of schizophrenia. Likewise, inflammatory cytokines and chemokines disturb the integrity of the BBB that normally maintains the immune privileged status of the brain.…”

“…They play a role in viral sensing and alerting the immune system, precisely via the production of cytokines and chemokines, to attract immune cells to the site of the infection. It has been reported that CNS infection with CV‐B induces pro‐inflammatory cytokine production, infiltration of inflammatory cells through the BBB and gliosis 86,120‐123 . In some of these studies, CV‐B established a persistent infection in the CNS of mice 86,120 .…”

“…Regarding the role potentially played by CV‐B, some studies have described neurodevelopment aberrations as a result of CV‐B infection 20 46 , 133 Furthermore, CV‐B infections during prenatal or perinatal period induce secretion of high levels of cytokines particularly type I interferons, TNFα, IL‐1β, IL‐6, and chemokines such as MCP‐1 and RANTES 86,120 . Disordered cytokine production during the critical stage of foetal life and perinatal period is a potential mechanism to affect the course of brain development causing abnormalities associated with schizophrenia.…”