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Tissue-specific immunopathology during malaria infection

Nature Reviews Immunology volume 18, pages 266–278 (2018)Cite this article

Subjects

Key Points

  • During blood-stage infections, Plasmodium parasites infect erythrocytes and can cause a variety of acute and chronic complications, some of which can be fatal. Although malaria complications are often attributed to sepsis-like systemic inflammation, the parasites in the circulation reach and interact with host tissues locally and specifically.

  • The brain, eye (retina), gastrointestinal tract, bones, lungs, kidneys and placenta are the organs that are specifically affected both during and even long after malaria infection. The unique anatomical structure of the vessels, parenchyma and lymphatics in each organ shapes the interaction with Plasmodium parasites and their products.

  • In the brain, unique areas such as the olfactory bulb, retina and perivascular spaces share similar anatomical and immunological features; Plasmodium parasites and their associated inflammation cause blood–brain barrier disruption in these areas.

  • The gastrointestinal tract microenvironment is a target of Plasmodium parasites and related events. Malaria infection causes the disruption of blood vessels and epithelial barriers in the gut.

  • Plasmodium parasites can reside in the bone marrow. At this site, the parasites and their products, such as haemozoin, interact with bone marrow niches and with cells resident in the bone tissue, including osteoblasts and osteoclasts, causing long-term effects in the host, such as bone loss.

  • The interactions that occur between Plasmodium parasites and the specific host tissues alter the outcome of malaria disease. A better understanding of malaria pathology in the context of host–parasite interactions at the various tissue levels of each organ will allow for better diagnostics and treatments for malaria.

Abstract

Systemic inflammation mediated by Plasmodium parasites is central to malaria disease and its complications. Plasmodium parasites reside in erythrocytes and can theoretically reach all host tissues via the circulation. However, actual interactions between parasitized erythrocytes and host tissues, along with the consequent damage and pathological changes, are limited locally to specific tissue sites. Such tissue specificity of the parasite can alter the outcome of malaria disease, determining whether acute or chronic complications occur. Here, we give an overview of the recent progress that has been made in understanding tissue-specific immunopathology during Plasmodium infection. As knowledge on tissue-specific host–parasite interactions accumulates, better treatment modalities and targets may emerge for intervention in malaria disease.

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Figure 1: Outcomes of Plasmodium infection of red blood cells in the bloodstream.
Figure 2: Interaction of Plasmodium-infected red blood cells with various blood vessels and lymphatics.
Figure 3: Infected red blood cells in close proximity with brain components.
Figure 4: Infected red blood cells in gut and bone marrow niches.

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Acknowledgements

The authors are supported by Grants-in-Aid for Scientific Research (B grant no. 16H05181 to C.C.) and by the Japan Agency for Medical Research and Development (AMED J-PRIDE 17fm0208021h0001 to C.C.).

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Authors and Affiliations

  1. Laboratory of Malaria Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, 565-0871, Japan

    Cevayir Coban & Michelle Sue Jann Lee

  2. Laboratory of Adjuvant Innovation, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, 567-0085, Japan

    Ken J. Ishii

  3. Laboratory of Vaccine Science, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, 565-0871, Japan

    Ken J. Ishii

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  1. Cevayir Coban
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  2. Michelle Sue Jann Lee
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C.C. wrote the manuscript; all authors contributed to researching data, discussing the content and reviewing and editing the manuscript.

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Correspondence to Cevayir Coban.

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PowerPoint slides

Glossary

Malaria

A disease caused by Plasmodium parasites belonging to the Apicomplexa phylum, which consists of several obligate intracellular parasites. The term was originally used in Italian folk medicine to mean poisonous or bad air.

Activation-induced cytidine deaminase

(AID). An enzyme that is required for two crucial B cell events in the germinal centre: somatic hypermutation and class-switch recombination.

Connective tissue

A connecting and supporting tissue composed of collagen and/or elastin fibres and interstitial fluid. Blood, bone and adipose tissue are some of the connective tissue components.

Perivascular spaces

Also known as Virchow–Robin spaces. Spaces located between brain-penetrating pial vessels and the brain tissue grey matter.

Interstitial fluid

(ISF). The solution present extracellularly, that fills the spaces between cells and tissues.

Cerebrospinal fluid

(CSF). The solution surrounding the brain and spinal cord, which mainly serves to protect these two important organs.

Olfactory bulb

An organ located on the cribriform plate, which functions in smell. The bulb surface is surrounded by complex olfactory nerve structures that originate from the nasal cavity and project to the brain. Small trabecular capillary structures are the main vessel structures inside the bulb.

Cribriform plate

A small, perforated bone structure that lies on top of the nasal cavity and supports the olfactory bulb. Olfactory nerves running from the nasal cavity to the olfactory bulb pass thorough cribriform plate.

Neurovascular coupling

A mechanism explaining the relationship between neuronal activity and the cerebral blood vessels and the blood flow.

Lacteals

Small lymphatic capillaries located in the villi of the small intestine.

Sinusoids

Vessels with a structure similar to capillaries but that have larger diameters and porous endothelial cells, which allow for permeability and exchange of materials; they are located in bone marrow, liver and spleen.

Haemozoin

A unique by-product of Plasmodium parasites that accumulates in several organs, including spleen, liver and bone marrow, even after the infection resolves.

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Coban, C., Lee, M. & Ishii, K. Tissue-specific immunopathology during malaria infection. Nat Rev Immunol 18, 266–278 (2018). https://doi.org/10.1038/nri.2017.138

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