Dual function of Ccr5 during langat virus encephalitis: Reduction in neutrophil-mediated central nervous system inflammation and increase in t cell-mediated viral clearance

Daniela Michlmayr, Susana V. Bardina, Carlos A. Rodriguez, Alexander G. Pletnev, Jean K. Lim

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Tick-borne encephalitis virus (TBEV) is a vector-transmitted flavivirus that causes potentially fatal neurologic infection. There are thousands of cases reported annually, and despite the availability of an effective vaccine, the incidence of TBEV is increasing worldwide. Importantly, up to 30% of affected individuals develop long-term neurologic sequelae.We investigated the role of chemokine receptor Ccr5 in a mouse model of TBEV infection using the naturally attenuated tick-borne flavivirus Langat virus (LGTV). Ccr5-deficient mice presented with an increase in viral replication within the CNS and decreased survival during LGTV encephalitis compared with wild-type controls. This enhanced susceptibility was due to the temporal lag in lymphocyte migration into the CNS. Adoptive transfer of wild-type T cells, but not Ccr5-deficient T cells, significantly improved survival outcome in LGTVinfected Ccr5-deficient mice. Concomitantly, a significant increase in neutrophil migration into the CNS in LGTV-infected Ccr52/2 mice was documented at the late stage of infection. Ab-mediated depletion of neutrophils in Ccr52/2 mice resulted in a significant improvement in mortality, a decrease in viral load, and a decrease in overall tissue damage in the CNS compared with isotype control-treated mice. Ccr5 is crucial in directing T cells toward the LGTV-infected brain, as well as in suppressing neutrophil-mediated inflammation within the CNS.

Original languageEnglish
Pages (from-to)4622-4631
Number of pages10
JournalJournal of Immunology
Volume196
Issue number11
DOIs
StatePublished - 1 Jun 2016

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