Proinflammatory Cytokines and Chemokines in Humans with Japanese Encephalitis

Winter, P.; Dung, Nguyen Minh; Loan, Ha Thi; Kneen, Rachel; Wills, Bridget; Thu, Le Thi Hien; House, Deborah; White, Nicholas J.; Farrar, Jeremy; Hart, C. A.; Solomon, Tom

doi:10.1086/423328

Cited by 180 publications

(184 citation statements)

References 38 publications

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“…Similar to CXCL8, an inverse correlation has been demonstrated for serum levels of CCL5 and survival among patients with JEV encephalitis [83]. This correlate for disease severity may contribute to pathogenesis, although the mechanism by which this occurs can only be speculated at this time.…”

Section: Ccl5mentioning

confidence: 95%

“…Although not well studied in mice, significant induction of CXCL8 was observed in patient serum and CSF, which corresponded with the presence of neutrophils in the CSF [72,79,82]. Notably, significantly higher levels of CXCL8 were associated with patient mortality [82,83]. Currently, no mouse studies have addressed the specific role of neutrophils in the context of JEV; however, these cells may be quite pathogenic.…”

Section: Cxcl8mentioning

confidence: 99%

“…In vitro work has demonstrated that microglia and astrocytes are the main cells that produce CCL5 during JEV infection [84]. In mice, microarray analysis shows an upregulation of CCL5 in the brain of JEV-infected mice [83,85]. Given the critical role of CCR5 in WNV, a role for this receptor in host defense in a mouse model of JEV should be tested, along with in vivo neutralization of CCL5.…”

Section: Ccl5mentioning

confidence: 99%

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The role of chemokines in the pathogenesis of neurotropic flaviviruses

Bardina

Lim

2012

Immunol Res

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Neurotropic flaviviruses are important emerging and reemerging arthropod-borne pathogens that cause significant morbidity and mortality in humans and other vertebrates worldwide. Upon entry and infection of the CNS, these viruses can induce a rapid inflammatory response characterized by the infiltration of leukocytes into the brain parenchyma. Chemokines and their receptors are involved in coordinating complex leukocyte trafficking patterns that regulate viral pathogenesis in vivo. In this review, we will summarize the current literature on the role of chemokines in regulating the pathogenesis of West Nile, Japanese encephalitis, and tick-borne encephalitis virus infections in mouse models and humans. Understanding how viral infections trigger chemokines, the key cellular events that occur during the infection process, as well as the immunopathogenic role of these cells, are critical areas of research that may ultimately guide a much needed effort toward developing specific immunomodulators and/or antiviral therapeutics.

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Section: Ccl5mentioning

confidence: 95%

Section: Cxcl8mentioning

confidence: 99%

Section: Ccl5mentioning

confidence: 99%

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The role of chemokines in the pathogenesis of neurotropic flaviviruses

Bardina

Lim

2012

Immunol Res

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“…In humans and other vertebrate animals, activated T cells that infiltrate the CNS during encephalitic DNA or RNA viral infections up-regulate expression of the chemokine receptors CCR1, CCR2, CCR5, and CXCR3 and their chemokine ligands CCL2 (CCR2), CCL3 (CCR1, CCR5), CCL4 (CCR5), CCL5 (CCR1, CCR5), and CXCL9 -CXCL11 (CXCR3) (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Although targeted deletion of CXCR3 or CXCL10 is associated with a reduction in infiltrating mononuclear cells and enhanced mortality from infection of the CNS with mouse hepatitis virus (MHV) 3 (25,26), few studies have examined regional differences in the expression of chemokine ligands during viral encephalitis.…”

Section: T He Infiltration Of Virus-specific Cd8 T Cells Is Essentialmentioning

confidence: 99%

CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis

Zhang

Chan

Liu

et al. 2008

The Journal of Immunology

163

147

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Regional differences in inflammation during viral infections of the CNS suggest viruses differentially induce patterns of chemoattractant expression, depending on their cellular targets. Previous studies have shown that expression of the chemokine CXCL10 by West Nile virus (WNV)-infected neurons is essential for the recruitment of CD8 T cells for the purpose of viral clearance within the CNS. In the current study we used mice deficient for the CXCL10 receptor, CXCR3, to evaluate its role in leukocyte-mediated viral clearance of WNV infection within various CNS compartments. WNV-infected CXCR3-deficient mice exhibited significantly enhanced mortality compared with wild-type controls. Immunologic and virologic analyses revealed that CXCR3 was dispensable for control of viral infection in the periphery and in most CNS compartments but, surprisingly, was required for CD8 T cell-mediated antiviral responses specifically within the cerebellum. WNV-specific, CXCR3-expressing T cells preferentially migrated into the cerebellum, and WNV-infected cerebellar granule cell neurons expressed higher levels of CXCL10 compared with similarly infected cortical neurons. These results indicate that WNV differentially induces CXCL10 within neuronal populations and suggest a novel model for nonredundancy in chemokine-mediated inflammation among CNS compartments.

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“…CCL5 was also detected in JEV-infected neuroblastoma cells, indicating a possible role for this chemokine in the early stages of infection. Interestingly, neuronal death and mortality rate increases in patients with elevated levels of proinflammatory cytokines and chemokines, including CCL5, in the serum and cerebrospinal fluid (Winter et al, 2004). Whether this is simply correlative data or whether these chemokines actually contribute to pathogenesis is currently unknown.…”

Section: Chemokines and Jev-associated Encephalitismentioning

confidence: 99%