Key Points
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Both innate and adaptive immune mechanisms that are elicited during malaria can prevent or cause disease and fatalities.
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Life-threatening malaria can present as diverse syndromes, which seem to confound the identification of unifying mechanisms of disease.
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Common themes in malaria pathogenesis, however, include the specific properties of parasitized red blood cells, the local and systemic action of bioactive toxins, and inappropriate inflammatory cascades initiated in target organs.
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The cerebral-malaria and severe-malarial-anaemia syndromes, in particular, seem to involve dysregulation of immune responses.
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We review the molecules that are involved in recognition of the parasite by the host and the cell–cell interactions that occur during the host immune response that might underlie pathogenesis.
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The contribution of immune mechanisms to fatalities from malaria has implications for vaccine design.
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Experimental models that recapitulate appropriate disease processes should be used in the preclinical assessment of candidate vaccines against malaria.
Abstract
Malaria is possibly the most serious infectious disease of humans, infecting 5–10% of the world's population, with 300–600 million clinical cases and more than 2 million deaths annually. Adaptive immune responses in the host limit the clinical impact of infection and provide partial, but incomplete, protection against pathogen replication; however, these complex immunological reactions can contribute to disease and fatalities. So, appropriate regulation of immune responses to malaria lies at the heart of the host–parasite balance and has consequences for global public health. This Review article addresses the innate and adaptive immune mechanisms elicited during malaria that either cause or prevent disease and fatalities, and it considers the implications for vaccine design.
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Acknowledgements
We thank A. Craig, V. Combes, N. Coltel, D. Hansen and K. Evans for useful discussion. This work was supported by the National Health and Medical Research Council (Australia), the National Institutes of Health (United States), the Human Frontier Science Program (France), the United Nations Children's Fund–United Nations Development Programme–World Bank–World Health Organization Special Programme for Research and Training in Tropical Diseases (Switzerland), the Paludisme+ programme of the French Ministry of Research (France), the Direction Générale des Armées (France), the Fondation Recherche Médicale (France) and the Wellcome Trust (United Kingdom). L.S. is an international research scholar of the Howard Hughes Medical Institute (United States).
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DATABASES
Entrez Gene
P-selectin glycoprotein ligand 1
Infectious disease information
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Glossary
- CHAGAS' DISEASE
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A disease that is caused by Trypanosoma cruzi. In chronic cases, it is associated with autoimmune damage to various organs.
- ERYTHROPOIETIC SUPPRESSION
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The inhibition of normal production of fresh red blood cells in the bone marrow or spleen. This occurs by various mechanisms, including inhibition of precursor-cell responsiveness to erythropoietin.
- NUDE MICE
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Mice with a mutation that causes both hairlessness and defective formation of the thymus, which results in a lack of mature T cells.
- RETICULOENDOTHELIAL SYSTEM
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The general phagocytic system of the host. It is responsible for removal and destruction of foreign material and senescent or dead host cells, such as red blood cells.
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Schofield, L., Grau, G. Immunological processes in malaria pathogenesis. Nat Rev Immunol 5, 722–735 (2005). https://doi.org/10.1038/nri1686
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DOI: https://doi.org/10.1038/nri1686
