Emerging Role of Splenic Macrophage in Malaria Pathogenesis and Immunity

Abstract

Background: 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.

Aim: 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.

Method: 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.

Result: 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.

Conclusion: 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.

Keywords: CD47; SIRPα; cytokines; macrophage; malaria; phagocytosis; polarization.

Figure 1

Comparative localization and functional specialization of splenic macrophage subsets in mouse and human spleens during malaria pathogenesis. (Created with Bio Render.com.)

Figure 2

Immunological mechanisms by which splenic macrophages contribute to malaria pathogenesis control. (Created with Bio Render.com.)

Figure 3

Continuum macrophage polarization spectrum of splenic macrophages during malaria pathogenesis, illustrating M1 and M2 subtypes characterized by distinct biomarkers and biological functions. Orange and green right triangles represent pro‐inflammatory and anti‐inflammatory cytokines levels, respectively. (Created with Bio Render.com.)