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In Vivo Infection with Leishmania amazonensis to Evaluate Parasite Virulence in Mice
Published on: February 20, 2020
CD100/Sema4D Increases Macrophage Infection by Leishmania (Leishmania) amazonensis in a CD72 Dependent Manner
Mariana K Galuppo1, Eloiza de Rezende1, Fabio L Forti2
1Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Abstract:
Leishmaniasis is caused by trypanosomatid protozoa of the genus Leishmania, which infect preferentially macrophages. The disease affects 12 million people worldwide, who may present cutaneous, mucocutaneous or visceral forms. Several factors influence the form and severity of the disease, and the main ones are the Leishmania species and the host immune response. CD100 is a membrane bound protein that can also be shed. It was first identified in T lymphocytes and latter shown to be induced in macrophages by inflammatory stimuli. The soluble CD100 (sCD100) reduces migration and expression of inflammatory cytokines in human monocytes and dendritic cells, as well as the intake of oxidized low-density lipoprotein (oxLDL) by human macrophages. Considering the importance of macrophages in Leishmania infection and the potential role of sCD100 in the modulation of macrophage phagocytosis and activation, we analyzed the expression and distribution of CD100 in murine macrophages and the effects of sCD100 on macrophage infection by Leishmania (Leishmania) amazonensis. Here we show that CD100 expression in murine macrophages increases after infection with Leishmania. sCD100 augments infection and phagocytosis of Leishmania (L.) amazonensis promastigotes by macrophages, an effect dependent on macrophage CD72 receptor. Besides, sCD100 enhances phagocytosis of zymosan particles and infection by Trypanosoma cruzi.
Insights
Soluble CD100 (sCD100) increases macrophage infection by Leishmania parasites. This effect is mediated by the CD72 receptor, highlighting sCD100 as a potential therapeutic target for leishmaniasis.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Leishmaniasis is a significant global health concern caused by Leishmania protozoa, primarily infecting macrophages.
- The disease presents in various forms (cutaneous, mucocutaneous, visceral), influenced by Leishmania species and host immunity.
- CD100, a protein found on lymphocytes and induced in macrophages, exists in membrane-bound and soluble forms (sCD100).
Purpose of the Study:
- To investigate CD100 expression in murine macrophages during Leishmania infection.
- To determine the impact of soluble CD100 (sCD100) on macrophage susceptibility to Leishmania (L.) amazonensis infection.
- To explore the role of the CD72 receptor in mediating sCD100 effects on macrophages.
Main Methods:
- Analysis of CD100 expression in murine macrophages post-Leishmania infection.
- In vitro experiments assessing the effect of sCD100 on macrophage phagocytosis of Leishmania promastigotes.
- Evaluation of sCD100's influence on macrophage uptake of zymosan particles and Trypanosoma cruzi infection.
Main Results:
- CD100 expression in murine macrophages significantly increases following Leishmania infection.
- sCD100 enhances both the phagocytosis of Leishmania (L.) amazonensis promastigotes and subsequent macrophage infection.
- This augmentation of infection by sCD100 is dependent on the presence of the CD72 receptor on macrophages.
- sCD100 also boosts the phagocytosis of zymosan particles and enhances Trypanosoma cruzi infection in macrophages.
Conclusions:
- Leishmania infection upregulates CD100 expression in macrophages.
- sCD100 promotes Leishmania infection and parasite uptake by macrophages, mediated through the CD72 receptor.
- These findings suggest sCD100 plays a role in modulating macrophage-parasite interactions and could be a target for therapeutic strategies against leishmaniasis and other parasitic infections.
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