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Published on: September 30, 2017
Strain-Dependent Immune Signaling by Small Extracellular Vesicles Derived From Trypanosoma cruzi-Infected Macrophages
Andrea C Mesías1, María Elisa Vázquez1, Maximiliano Cosenza2
1Instituto de Patología Experimental "Dr. Miguel Ángel Basombrío" (IPE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad Nacional de Salta, Salta, Argentina.
Abstract:
Among extracellular vesicles (EVs), exosomes, comprised within small EVs are bilayered nanovesicles carrying specific cargo that are released into the interstitial space in a highly regulated manner. In this study, we investigated the message transmitted through macrophage-derived small EVs in response to the interaction with Trypanosoma cruzi, the protozoan responsible for Chagas disease. We utilized two distinct parasite strains, the virulent CL Brener and the attenuated TCC. When taken up by naϊve macrophages (Mφs) in vitro, small EVs derived from TCC-infected cells favor an adverse environment for parasite spread, with M1-like cytokine pattern. In contrast, EVs from CL Brener-infected cells fostered a more permissive environment with reduced TNF-α/IL-10 ratio, higher phagocytic activity and reduced migration capacity, which may hinder a timely immune response. Further, while naïve Mφs' EVs induced iNOS and nitric oxide (NO) secretion, EVs from T. cruzi-infected Mφs failed to robustly activate iNOS, suggesting the parasite may modulate EV-mediated communication to avoid NO toxicity. In vivo assays showed distinct parasitemia courses with higher parasite burden when mice were treated with small EVs from CL Brener-infected Mφs. Overall, small EVs released by infected Mφs serve as messengers in T. cruzi infection, inducing different immune responses based on parasite virulence.
Insights
Macrophage-derived small extracellular vesicles (EVs) transmit distinct messages during Trypanosoma cruzi infection. Virulent parasite strains promote immune evasion, while attenuated strains induce an anti-parasitic environment via EVs.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Extracellular vesicles (EVs), including exosomes, are key mediators of intercellular communication.
- Macrophage-derived small EVs play a role in modulating immune responses.
- Chagas disease, caused by Trypanosoma cruzi, presents a significant global health challenge.
Purpose of the Study:
- To investigate the role of macrophage-derived small EVs in Trypanosoma cruzi infection.
- To compare the effects of EVs from macrophages infected with virulent (CL Brener) versus attenuated (TCC) T. cruzi strains.
- To understand how parasite virulence influences EV-mediated communication and host immune response.
Main Methods:
- In vitro studies using naive macrophages (Mφs) and small EVs derived from T. cruzi-infected Mφs.
- Analysis of cytokine patterns (e.g., TNF-α, IL-10), phagocytic activity, and nitric oxide (NO) secretion.
- In vivo experiments in mice treated with small EVs from infected Mφs to assess parasitemia.
Main Results:
- EVs from TCC-infected Mφs created an adverse environment for parasite spread, promoting an M1-like cytokine profile.
- EVs from CL Brener-infected Mφs fostered a permissive environment, characterized by a reduced TNF-α/IL-10 ratio and impaired immune cell migration.
- T. cruzi infection modulated EV-mediated communication, potentially to evade NO toxicity, as infected Mφ-derived EVs showed reduced iNOS activation.
- In vivo, mice treated with EVs from CL Brener-infected Mφs exhibited higher parasite burdens.
Conclusions:
- Macrophage-derived small EVs act as crucial messengers in T. cruzi infection.
- The virulence of T. cruzi strains dictates the immune response elicited by these EVs.
- Parasite modulation of EV communication is a potential mechanism for immune evasion.
