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New Therapeutic Tools to Shape Monocyte Functional Phenotypes in Leishmaniasis
Natália S Vellozo1, Thaís S Rigoni1, Marcela F Lopes1
1Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Frontiers in Immunology
|July 12, 2021
Summary
Innate immunity to Leishmania infection involves macrophages and monocytes. This study explores how therapies like all-trans-retinoic acid (ATRA) and RANKL can target monocytes to fight Leishmania parasites.
Area of Science:
- Immunology
- Parasitology
- Infectious Diseases
Background:
- Innate immunity to Leishmania infection involves diverse immune cells, including macrophages, monocytes, neutrophils, and dendritic cells.
- Macrophages exhibit plasticity, shifting between M1 (antimicrobial) and M2 (parasite-permissive) phenotypes, influenced by host genetics, parasite species, and T-cell cytokines (Th1/IFN-γ and Th2/IL-4).
- While macrophage polarization is well-studied, the functional phenotypes of monocytes during Leishmania infection are an emerging area of research.
Purpose of the Study:
- To investigate the role of inflammatory monocytes in the innate immune response to Leishmania infection.
- To explore the potential of host-directed therapies, specifically all-trans-retinoic acid (ATRA) and Receptor Activator of Nuclear Factor-Kappa B ligand (RANKL), in modulating monocyte function.
- To determine if ATRA and RANKL can direct monocytes towards M1 or M2 phenotypes to enhance immunity against Leishmania parasites.
Main Methods:
- Review and synthesis of existing literature on innate immunity, Leishmania infection, macrophage and monocyte phenotypes.
- Analysis of the mechanisms by which inflammatory monocytes contribute to host defense or susceptibility.
- Evaluation of the potential immunomodulatory effects of ATRA and RANKL on monocyte polarization.
Main Results:
- Inflammatory monocytes play a critical role in the immune response to Leishmania, accumulating effector and efferocytosis functions.
- Macrophages display a spectrum of phenotypes (M1-M2) crucial for resistance or susceptibility to leishmaniasis.
- ATRA and RANKL show potential as therapeutic agents by directly targeting monocytes to influence M1/M2 polarization.
Conclusions:
- Inflammatory monocytes are key players in the innate immune response to Leishmania.
- Targeting monocyte differentiation into M1 or M2 phenotypes presents a promising strategy for host-directed therapies against leishmaniasis.
- Further research into ATRA and RANKL modulation of monocyte immunity could lead to novel treatments for leishmaniasis.
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