The NLRP3 inflammasome is involved with the pathogenesis of Mayaro virus

Luiza A de Castro-Jorge1, Renan V H de Carvalho1, Taline M Klein2

  • 1Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo. Ribeirão Preto, Brazil.

Plos Pathogens
|September 4, 2019
PubMed

Insights

Mayaro virus (MAYV) infection triggers the NLRP3 inflammasome, a key driver of inflammation and disease symptoms. This inflammasome activation is crucial for Mayaro fever pathogenesis in both cellular models and infected patients.

Area of Science:

  • Immunology
  • Virology
  • Pathogenesis

Background:

  • Mayaro virus (MAYV) is an emerging arbovirus causing Mayaro fever, a severe inflammatory disease.
  • MAYV infection presents with fever, rash, and prolonged arthralgia, posing a public health concern.
  • The pathogenesis and immune response to MAYV are poorly understood compared to other arboviruses.

Purpose of the Study:

  • To investigate the role of inflammasomes in Mayaro virus pathogenesis.
  • To elucidate the mechanisms of NLRP3 inflammasome activation by MAYV.
  • To assess the therapeutic potential of targeting the NLRP3 inflammasome in MAYV infection.

Main Methods:

  • Established MAYV infection models in bone marrow-derived macrophages and mice.
  • Utilized inflammasome-deficient (Nlrp3-/-, Aim2-/-, Asc-/-, Casp1/11-/-) mice for infection studies.
  • Measured cytokine production (IL-1β, IL-18) and inflammasome protein expression (NLRP3, ASC, AIM2, Caspase-1).
  • Assessed ROS production and potassium efflux in MAYV-infected macrophages.
  • Analyzed serum from MAYV-infected patients for inflammasome markers.

Main Results:

  • MAYV replicates in macrophages and induces inflammasome protein expression.
  • NLRP3 inflammasome, not AIM2, is essential for IL-1β production in MAYV-infected macrophages.
  • MAYV activates NLRP3 inflammasome via reactive oxygen species (ROS) and potassium efflux.
  • NLRP3 inflammasome deficiency in mice reduces footpad swelling, inflammation, and pain.
  • Elevated caspase-1, IL-1β, and IL-18 levels were detected in MAYV-infected patients.

Conclusions:

  • The NLRP3 inflammasome plays a critical role in Mayaro virus pathogenesis.
  • NLRP3 inflammasome activation contributes to the inflammatory symptoms of Mayaro fever.
  • Targeting the NLRP3 inflammasome could be a therapeutic strategy for MAYV infections.

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