期刊
EMBO MOLECULAR MEDICINE
卷 10, 期 1, 页码 121-138出版社
WILEY
DOI: 10.15252/emmm.201707885
关键词
CD8(+) T-cell trafficking; Chikungunya; co-infection; malaria
资金
- SIgN
- A*STAR
- Biomedical Research Council, A*STAR
- NUS Graduate School for Integrative Science and Engineering
- Agency for Science, Technology and Research (A*STAR)
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 gamma-mediated mechanism. Co-infection with CHIKV induced higher splenic IFN gamma 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.
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