Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that takes a significant toll on human life. Blockage of the brain blood vessels contributes to the clinical signs of CM, however we know little about the precise pathological events that lead to this disease. To this end, studies in Plasmodium-infected mice, that also develop a similar fatal disease, have proven useful. These studies have revealed an important role for leukocytes not so much in protecting but rather promoting pathology in the brain. To better understand leukocyte behaviour during experimental CM, we established a brain-imaging model that allows us to ‘peek’ into the brain of living mice and watch immunological events as they unfold. We found that worsening of disease was accompanied by an accumulation of monocytes in the blood vessels. Monocyte accumulation was regulated by activated CD8+ T cells but only when present in critical numbers. Monocyte depletion resulted in reduced T cell trafficking to the brain, but this did not result in improved disease outcome. Our studies reveal the orchestration of leukocyte accumulation in real time during CM, and demonstrate that CD8+ T cells play a crucial role in promoting clinical signs in this disease.
Vyšlo v časopise: Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004236 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004236
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