Platelet-derived DKK1 enhances leukocyte-platelet aggregation and recruits immune cells in Leishmaniasis models

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Frontiers in Medicine Published June 3, 2026 Medically reviewed June 3, 2026 Study authors: Olivia C. Ihedioha, Diane McMahon-Pratt, Alfred L. M. Bothwell DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider platelet-derived DKK1 as a potential immunomodulatory target in Leishmaniasis models.

This review investigates the immunomodulatory functions of platelet-derived DKK1 in the context of Leishmaniasis. The analysis is based on data from BALB/c mice, where the intervention involved platelet-derived DKK1. The authors describe several observed effects without reporting specific numerical values or statistical significance. The findings indicate that leukocyte-platelet aggregation was enhanced during the process. Additionally, the recruitment of neutrophils, macrophages, and dendritic cells was observed. The review also notes a contribution to dendritic cell polarization favoring cDC2 and DC-10-mediated T-cell differentiation. Furthermore, M2 macrophage polarization and intracellular parasite survival were noted as areas of contribution. Conversely, Th1-associated responses were reported as diminished in this model system. The authors did not report adverse events or discontinuations as these details were not available in the source material. The practice relevance is identified as a potential immunomodulatory target. However, the authors highlight a limitation regarding the need for further studies to clarify its translational relevance across infectious diseases. The review does not provide specific p-values or confidence intervals for these outcomes.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

Parasitic infection caused by Leishmania major in BALB/c mice is a well-established example of a chronic inflammatory disease. Although chronic inflammation in parasitic infections stems from persistent interactions between parasites and host immune cells, the mechanisms by which parasitic infections induce and regulate chronic immune responses remain to be fully understood. Emerging evidence suggests that platelets contribute not only to hemostasis but also modulate immune response during infection and inflammation. This review examines the emerging role of platelet-derived Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, in shaping immunity during cutaneous leishmaniasis and explores its broader implications in other infectious diseases. Experimental findings from BALB/c mouse models indicate that Leishmania major infection promotes platelet activation and DKK1 release, leading to enhanced leukocyte-platelet aggregation and recruitment of neutrophils, macrophages, and dendritic cells to inflammatory sites. Platelet-derived DKK1 appears to influence dendritic cell polarization, favoring cDC2 and DC-10-mediated T-cell differentiation associated with Th2 and regulatory immune responses which contribute to M2 macrophage polarization and intracellular parasite survival. In contrast, protective antileishmanial Th1-associated responses may be diminished in the presence of sustained DKK1 signaling. Thus, this review integrates current evidence indicating that platelet-derived DKK1 functions as an early regulator of both innate and adaptive immune responses during Leishmania infection. Beyond leishmaniasis, accumulating evidence suggests that platelet activation and DKK1 release may also participate in the immunopathology of fungal and viral infections. By integrating current evidence on platelet-mediated immune regulation, this review highlights platelet-derived DKK1 as a potential immunomodulatory target and emphasizes the need for further studies to clarify its translational relevance across infectious diseases.