# Emerging Role of Splenic Macrophage in Malaria Pathogenesis and Immunity

## TL;DR

This paper reviews how splenic macrophages influence malaria immunity and could help develop better treatments and vaccines.

## Contribution

The paper highlights the dual and dynamic role of splenic macrophages in malaria and their potential as therapeutic targets.

## Key findings

- Splenic macrophages modulate immune responses by balancing pro- and anti-inflammatory functions during malaria.
- Macrophage polarization is not strictly dichotomous but exists along a continuum during Plasmodium infection.
- Targeting macrophage functions could improve vaccine development and treatment strategies for malaria.

## Abstract

Malaria, caused by Plasmodium parasites, remains a leading global health concern, impacting millions of people globally. Splenic macrophages are specialized immune cells that reside in the spleen and play a pivotal role in the pathogenesis and immune response during malaria. These cells are fundamental to the body's defense against Plasmodium due to their multifaceted roles in parasite clearance, antigen presentation, and immune regulation. They participate in the early immune response by phagocytosing infected red blood cells, producing cytokines, and interacting with other immune cells to modulate both pro‐inflammatory and anti‐inflammatory responses.

This review highlights the evolving understanding of splenic macrophages in malaria pathogenesis and immunity and underscores their importance in the development of novel therapeutic interventions.

The search strategy included retrieving relevant studies from PubMed Central and Google Scholar spanning between 1955–2025. Articles were screened based on relevance to malaria immunology, macrophage biology, and therapeutic interventions. Both experimental and clinical studies were considered, and references from selected articles were also cross‐checked to identify additional relevant literature. Priority was given to peer‐reviewed articles, systematic reviews, and original research that provided insights into the immunological role of splenic macrophages in malaria.

Splenic macrophages play a dual role in disease progression and severity. They have a specialized ability to polarize into different functional states under different microenvironments. Notably, macrophage polarization during Plasmodium infection is not strictly dichotomous but exists along a continuum, with macrophages exhibiting both M1 and M2 characteristics, facilitating dynamic immune modulation. This continuum of polarization is essential for balancing immune responses and ensuring effective immunity while avoiding excessive inflammation. Emerging evidence suggests that splenic macrophages significantly influence malaria severity and clinical outcomes, positioning them as key targets for therapeutic strategies.

Optimizing macrophage‐mediated immunity by targeting specific macrophage functions and biomarkers could hold promise for improving vaccine development, diagnostics, prognosis, and treatment strategies, thereby enhancing clinical outcomes for malaria patients.

Splenic macrophages play a crucial role in providing immunity during malaria pathogenesis.Different Plasmodium strains have different impact on splenic macrophages during infection.Splenic macrophages contribute toward immune defense through various mechanisms such as by engaging in phagocytosis, facilitating ADCI (antibody‐dependent cellular inhibition) and through release of cytokines.Emphasizing the role of splenic macrophages in cellular and humoral immune response could enhance strategies for effective vaccine development.Enhancing macrophage‐mediated immunity can lead to advancements in diagnosis, prognosis, and treatment approaches for malaria.

Splenic macrophages play a crucial role in providing immunity during malaria pathogenesis.

Different Plasmodium strains have different impact on splenic macrophages during infection.

Splenic macrophages contribute toward immune defense through various mechanisms such as by engaging in phagocytosis, facilitating ADCI (antibody‐dependent cellular inhibition) and through release of cytokines.

Emphasizing the role of splenic macrophages in cellular and humoral immune response could enhance strategies for effective vaccine development.

Enhancing macrophage‐mediated immunity can lead to advancements in diagnosis, prognosis, and treatment approaches for malaria.