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Monocyte epigenetics and innate immunity to malaria: yet another level of complexity?
Katherine R Dobbs1, Arlene E Dent1, Paula Embury2
1Centre for Global Health and Diseases, Case Western Reserve University, 10900 Euclid Avenue LC:4983, Cleveland, OH 44106, USA; Division of Pediatric Infectious Diseases, Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA.
Insights
In areas with high malaria transmission, young children get sick, while older children often have asymptomatic infections. Host epigenetic changes in monocytes/macrophages may explain this difference in malaria presentation.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Children under 5 in high malaria transmission areas often develop clinical malaria with fever.
- Older children in similar areas frequently have subclinical malaria (chronic Plasmodium falciparum infection without symptoms).
- The innate immune system's role in balancing parasite control and disease tolerance in subclinical malaria is unclear.
Purpose of the Study:
- To explore the role of host epigenetic mechanisms in innate immune homeostasis during subclinical malaria.
- To present evidence that epigenetic modifications in monocytes/macrophages are key to regulating immune functions in subclinical malaria.
Main Methods:
- This is a Current Opinion article, presenting a review and synthesis of recent studies.
- Focuses on evidence related to epigenetic modifications in host immune cells.
Main Results:
- Recent studies suggest host epigenetic mechanisms are involved in the immune homeostasis of subclinical malaria.
- Evidence supports the idea that epigenetic modifications in monocytes/macrophages regulate innate immune functions relevant to subclinical malaria.
Conclusions:
- Epigenetic regulation of the monocyte/macrophage epigenome is a critical factor in the development of subclinical malaria.
- Understanding these mechanisms could offer new insights into managing malaria in endemic regions.
Abstract:
Children under the age of 5 years living in areas of moderate to high malaria transmission are highly susceptible to clinical malaria with fever that prompts treatment of blood stage infection with anti-malarial drugs. In contrast, older school age children frequently experience subclinical malaria, i.e. chronic Plasmodium falciparum parasitemia without fever or other clinical symptoms. The role of innate immune cells in regulating inflammation at a level that is sufficient to control the parasite biomass, while at the same time maintaining a disease-tolerant clinical phenotype, i.e., subclinical malaria, is not well understood. Recent studies suggest that host epigenetic mechanisms underlie the innate immune homeostasis associated with subclinical malaria. This Current Opinion article presents evidence supporting the notion that modifications of the host monocyte/macrophage epigenome regulate innate immune functions pertinent to subclinical malaria.
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