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Updated: Apr 20, 2026

In Vitro Assay of Plasmodium-Infected Red Blood Cell Killing by Cytotoxic Lymphocytes
Published on: August 17, 2022
The case for exploring innate memory in Plasmodium infection
Nhi Nt Ho1, Tinotenda Tongogara2, Tuan M Tran3
1University of Washington, Pathobiology Doctoral Program, Department of Global Health, School of Medicine, Seattle, WA, USA; Seattle Children's Research Institute, Center for Global Infectious Disease Research, Seattle, WA, USA.
Abstract:
In highly malaria-endemic areas, individuals can receive a bite from a Plasmodium-infected mosquito daily. Yet, most studies in the laboratory only assess a single infection, and our current understanding of malaria immunity does not fully explain how recurrent infections in the field impact pathogenesis and immunity upon re-infection. A growing body of literature suggests innate immune memory, in which epigenetic reprogramming regulates the immune response to sequential infections independently of adaptive immunity, may explain some of the dynamics of recurring Plasmodium infection in endemic areas. Here, we summarize the basic concepts of innate immune memory and findings that support its role in controlling Plasmodium infection and pathogenesis. Furthermore, we postulate that innate memory in non-immune cells, which is only beginning to be described in other disease systems, may have significant consequences in the context of the complex Plasmodium lifecycle.
Insights
In malaria-endemic regions, daily Plasmodium infections may be controlled by innate immune memory. This epigenetic reprogramming of immune responses offers a new perspective on recurring infections and disease progression.
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- Individuals in malaria-endemic areas face daily bites from Plasmodium-infected mosquitoes.
- Laboratory studies typically focus on single infections, limiting understanding of immunity during recurrent Plasmodium infections.
- Current malaria immunity models do not fully explain pathogenesis and immune responses upon re-infection in endemic settings.
Purpose of the Study:
- To summarize innate immune memory concepts relevant to Plasmodium infection.
- To review evidence supporting innate immune memory's role in controlling Plasmodium infection and pathogenesis.
- To explore the potential impact of innate memory in non-immune cells on the Plasmodium lifecycle.
Main Methods:
- Literature review and synthesis of existing research on innate immune memory.
- Analysis of findings related to Plasmodium infection and pathogenesis.
- Postulation of innate memory's role in non-immune cells within the Plasmodium lifecycle.
Main Results:
- Innate immune memory, involving epigenetic reprogramming, may regulate responses to sequential Plasmodium infections independently of adaptive immunity.
- Existing literature suggests innate immune memory contributes to controlling Plasmodium infection and pathogenesis.
- Innate memory in non-immune cells is an emerging concept with potential implications for malaria.
Conclusions:
- Innate immune memory offers a potential explanation for the dynamics of recurrent Plasmodium infections in endemic areas.
- Further research into innate memory, particularly in non-immune cells, is warranted to understand its full impact on malaria.
- Understanding innate immune memory could lead to novel strategies for managing malaria pathogenesis and immunity.
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