Immunomodulation by platelet-derived DKK1: potential for controlling disease and pathology in leishmaniasis and implications for other infectious diseases

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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