Co-infection with Chikungunya virus alters trafficking of pathogenic CD8(+) T cells into the brain and prevents Plasmodium-induced neuropathology



Teo, Teck-Hui, Howland, Shanshan W, Claser, Carla, Gun, Sin Yee, Poh, Chek Meng, Lee, Wendy WL, Lum, Fok-Moon, Ng, Lisa FP ORCID: 0000-0003-4071-5222 and Renia, Laurent
(2018) Co-infection with Chikungunya virus alters trafficking of pathogenic CD8(+) T cells into the brain and prevents Plasmodium-induced neuropathology. EMBO MOLECULAR MEDICINE, 10 (1). 121 - 138.

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Abstract

Arboviral diseases have risen significantly over the last 40 years, increasing the risk of co‐infection with other endemic disease such as malaria. However, nothing is known about the impact arboviruses have on the host response toward heterologous pathogens during co‐infection. Here, we investigate the effects of Chikungunya virus (CHIKV ) co‐infection on the susceptibility and severity of malaria infection. Using the Plasmodium berghei ANKA (PbA) experimental cerebral malaria (ECM ) model, we show that concurrent co‐infection induced the most prominent changes in ECM manifestation. Concurrent co‐infection protected mice from ECM mortality without affecting parasite development in the blood. This protection was mediated by the alteration of parasite‐specific CD8+ T‐cell trafficking through an IFN γ‐mediated mechanism. Co‐infection with CHIKV induced higher splenic IFN γ levels that lead to high local levels of CXCL 9 and CXCL 10. This induced retention of CXCR 3‐expressing pathogenic CD8+ T cells in the spleen and prevented their migration to the brain. This then averts all downstream pathogenic events such as parasite sequestration in the brain and disruption of blood–brain barrier that prevents ECM ‐induced mortality in co‐infected mice.

Item Type: Article
Uncontrolled Keywords: CD8(+) T-cell trafficking, Chikungunya, co-infection, malaria
Depositing User: Symplectic Admin
Date Deposited: 22 Feb 2018 09:23
Last Modified: 16 Sep 2022 03:10
DOI: 10.15252/emmm.201707885
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3018320