Interferon Regulatory Factor 1 is essential for pathogenic CD8+ T cell migration and retention in the brain during experimental cerebral malaria

Abstract Host immune response has a key role in controlling the progression of malaria infection. In the well‐established murine model of experimental cerebral malaria (ECM) with P. berghei ANKA infection, pro‐inflammatory Th1 and CD8+ T cells response are essential for disease development. Interferon regulatory factor 1 (IRF1) is a transcription factor which promotes Th1 responses and its absence was previously shown to protect from ECM death. Yet, the exact mechanism of protection remains unknown. Here we demonstrated that IRF1‐deficient mice (IRF1KO) were protected from ECM death despite displaying early neurological signs. Resistance to ECM death was a result of reduced parasite sequestration and pathogenic CD8+ T cells in the brain. Further analysis revealed that IRF1 deficiency suppress IFNγ production and delayed CD8+ T cell proliferation. CXCR3 expression was found to be decreased on pathogenic CD8+ T cells which limited their migration to the brain. In addition, reduced expression of adhesion molecules by brain endothelial cells hampered leukocyte retention in the brain. Taken together, these factors limited sequestration of pathogenic CD8+ T cells and consequently its ability to induce extensive damage to the blood‐brain barrier.
Source: Cellular Microbiology - Category: Microbiology Authors: Tags: RESEARCH ARTICLE Source Type: research