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

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 IFNγ‐mediated mechanism. Co‐infection with CHIKV induced higher splenic IFNγ levels that lead to high local levels of CXCL9 and CXCL10. This induced retention of CXCR3‐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.