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

Autor: Teo TH; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Howland SW; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Claser C; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Gun SY; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Poh CM; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Lee WW; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Lum FM; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Ng LF; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore lisa_ng@immunol.a-star.edu.sg renia_laurent@immunol.a-star.edu.sg.; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK., Rénia L; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore lisa_ng@immunol.a-star.edu.sg renia_laurent@immunol.a-star.edu.sg.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2018 Jan; Vol. 10 (1), pp. 121-138.
DOI: 10.15252/emmm.201707885
Abstrakt: 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.
(© 2017 Agency for Science, Technology and Research (A*STAR). Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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