| First Author | Palomo J | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 10 | Pages | 2683-95 |
| PubMed ID | 23780878 | Mgi Jnum | J:201696 |
| Mgi Id | MGI:5515283 | Doi | 10.1002/eji.201343327 |
| Citation | Palomo J, et al. (2013) Type I interferons contribute to experimental cerebral malaria development in response to sporozoite or blood-stage Plasmodium berghei ANKA. Eur J Immunol 43(10):2683-95 |
| abstractText | Cerebral malaria is a severe complication of Plasmodium falciparum infection. Although T-cell activation and type II IFN-gamma are required for Plasmodium berghei ANKA (PbA)-induced murine experimental cerebral malaria (ECM), the role of type I IFN-alpha/beta in ECM development remains unclear. Here, we address the role of the IFN-alpha/beta pathway in ECM devel-opment in response to hepatic or blood-stage PbA infection, using mice deficient for types I or II IFN receptors. While IFN-gammaR1(-/-) mice were fully resistant, IFNAR1(-/-) mice showed delayed and partial protection to ECM after PbA infection. ECM resistance in IFN-gammaR1(-/-) mice correlated with unaltered cerebral microcirculation and absence of ischemia, while WT and IFNAR1(-/-) mice developed distinct microvascular pathologies. ECM resistance appeared to be independent of parasitemia. Instead, key mediators of ECM were attenuated in the absence of IFNAR1, including PbA-induced brain sequestration of CXCR3(+) -activated CD8(+) T cells. This was associated with reduced expression of Granzyme B, IFN-gamma, IL-12Rbeta2, and T-cell-attracting chemokines CXCL9 and CXCL10 in IFNAR1(-/-) mice, more so in the absence of IFN-gammaR1. Therefore, the type I IFN-alpha/beta receptor pathway contributes to brain T-cell responses and microvascular pathology, although it is not as essential as IFN-gamma for the development of cerebral malaria upon hepatic or blood-stage PbA infection. |
