The NLRP3 inflammasome is involved with the pathogenesis of Mayaro virus.

Autor: de Castro-Jorge LA; Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., de Carvalho RVH; Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Klein TM; Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Hiroki CH; Center for Research in Inflammatory Diseases, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Lopes AH; Center for Research in Inflammatory Diseases, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Guimarães RM; Center for Research in Inflammatory Diseases, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Fumagalli MJ; Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Floriano VG; Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Agostinho MR; Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Slhessarenko RD; School of Medicine, Federal University of Mato Grosso, Cuiabá, Brazil., Ramalho FS; Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Cunha TM; Center for Research in Inflammatory Diseases, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Cunha FQ; Center for Research in Inflammatory Diseases, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., da Fonseca BAL; Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil., Zamboni DS; Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2019 Sep 03; Vol. 15 (9), pp. e1007934. Date of Electronic Publication: 2019 Sep 03 (Print Publication: 2019).
DOI: 10.1371/journal.ppat.1007934
Abstrakt: Mayaro virus (MAYV) is an arbovirus that circulates in Latin America and is emerging as a potential threat to public health. Infected individuals develop Mayaro fever, a severe inflammatory disease characterized by high fever, rash, arthralgia, myalgia and headache. The disease is often associated with a prolonged arthralgia mediated by a chronic inflammation that can last months. Although the immune response against other arboviruses, such as chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV), has been extensively studied, little is known about the pathogenesis of MAYV infection. In this study, we established models of MAYV infection in macrophages and in mice and found that MAYV can replicate in bone marrow-derived macrophages and robustly induce expression of inflammasome proteins, such as NLRP3, ASC, AIM2, and Caspase-1 (CASP1). Infection performed in macrophages derived from Nlrp3-/-, Aim2-/-, Asc-/-and Casp1/11-/-mice indicate that the NLRP3, but not AIM2 inflammasome is essential for production of inflammatory cytokines, such as IL-1β. We also determined that MAYV triggers NLRP3 inflammasome activation by inducing reactive oxygen species (ROS) and potassium efflux. In vivo infections performed in inflammasome-deficient mice indicate that NLRP3 is involved with footpad swelling, inflammation and pain, establishing a role of the NLRP3 inflammasome in the MAYV pathogenesis. Accordingly, we detected higher levels of caspase1-p20, IL-1β and IL-18 in the serum of MAYV-infected patients as compared to healthy individuals, supporting the participation of the NLRP3-inflammasome during MAYV infection in humans.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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