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Visualizing Macrophage Extracellular Traps Using Confocal Microscopy
Published on: October 19, 2017
DNA Extracellular Traps Released by Mayaro Virus-Infected Macrophages Act as a Platform for Virus Dissemination
Ana S Carvalho1, Gean Carlo Pereira-Silva2, Julia M P Andrade1
1Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract:
Mayaro virus (MAYV) is an arthritogenic arbovirus that causes a debilitating illness that can progress to a chronic rheumatic disease characterized by persistent viral replication in macrophages within joint tissues. Here, we report that MAYV-infected macrophages release decondensed DNA traps (DNA extracellular traps, DETs) through a mechanism driven by the production of reactive oxygen species and peptidyl arginine deiminase activation, resembling the classical mechanism of pathogen clearance by activated neutrophils. Unlike traditional pathogen clearance observed for NETs released by neutrophils, MAYV-induced DETs did not inactivate the virus. Instead, DET-ensnared viruses are internalized by neighboring uninfected macrophages, increasing the number of infected cells. Collectively, these findings suggest that MAYV-containing DETs act as a "Trojan horse" that facilitates viral dissemination within inflamed tissues, connecting macrophage-mediated inflammatory response to viral persistence in the articular tissue in chronic MAYV disease.
Insights
Mayaro virus (MAYV) causes chronic joint disease. Infected macrophages release DNA traps that spread the virus to new cells, promoting disease persistence.
Area of Science:
- Virology
- Immunology
- Rheumatology
Background:
- Mayaro virus (MAYV) causes arthritogenic illness and chronic rheumatic disease.
- Persistent MAYV replication occurs in macrophages within joint tissues.
Purpose of the Study:
- To investigate the mechanism of MAYV persistence in macrophages.
- To understand the role of macrophage-released DNA extracellular traps (DETs) in MAYV dissemination.
Main Methods:
- Analysis of MAYV-infected macrophages.
- Investigation of reactive oxygen species and peptidyl arginine deiminase activation.
- Assessment of MAYV-induced DNA extracellular traps (DETs) for viral inactivation and cell-to-cell spread.
Main Results:
- MAYV-infected macrophages release decondensed DNA traps (DETs) via reactive oxygen species and peptidyl arginine deiminase.
- Unlike neutrophil NETs, MAYV-induced DETs do not inactivate the virus.
- DET-ensnared MAYV is internalized by uninfected macrophages, increasing viral spread.
Conclusions:
- MAYV-induced DETs act as a "Trojan horse" facilitating viral dissemination in inflamed tissues.
- Macrophage DETs contribute to viral persistence in articular tissue during chronic MAYV disease.
- Connects macrophage inflammatory response to MAYV persistence.
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