| First Author | Teo TH | Year | 2018 |
| Journal | EMBO Mol Med | Volume | 10 |
| Issue | 1 | Pages | 121-138 |
| PubMed ID | 29113976 | Mgi Jnum | J:262436 |
| Mgi Id | MGI:6155569 | Doi | 10.15252/emmm.201707885 |
| Citation | Teo TH, et al. (2018) Co-infection with Chikungunya virus alters trafficking of pathogenic CD8(+) T cells into the brain and prevents Plasmodium-induced neuropathology. EMBO Mol Med 10(1):121-138 |
| abstractText | 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 IFNgamma-mediated mechanism. Co-infection with CHIKV induced higher splenic IFNgamma 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. |
