The NLRP3 inflammasome is involved with the pathogenesis of Mayaro virus
Fig 5
NLRP3 signaling participates in the pathogenesis of MAYV infection in vivo.
WT and Nlrp3–/–mice (n = 5 per injected group) were injected subcutaneously into the footpad with 10 μL of MAYV (105 or 106 PFU) or mock infected. Footpad thickness height (H) X width (W) was measured daily through to the 10th day of infection in mock (A) and MAYV-injected mice with 105 PFU dose (B) or 106 PFU dose (C). Representative images of paws at day 6 after infection are shown (D). WT, Nlrp3–/–(Genentech), Nlrp3–/–(Jackson), Caspase1/11-/- mice (n = 5 per injected group) were injected subcutaneously into the footpad with 10 μL of MAYV (105 PFU) or mock infected and footpad thickness was measured daily through to the 10th day of infection (E). The von-Frey test was used to measure pain in the paws of mock (F) and MAYV-injected mice (G). (H-J) WT and Nlrp3–/–mice were euthanized at 1 and 6 days after infection and the amount of MAYV RNA was quantified in the footpad (H), muscle (I) and spleen (J). Virus titers were determined in the same organs by plaque assay (K) and are represented as mean ± SD. WT, Nlrp3–/–and Casp1/11-/- mice were injected with Mock or MAYV for 5 days. Footpads were obtained, and both IL-1β (L) and IL-18 (M) were quantified in the homogenate’s supernatants. Data shown are representative of three (A-D) or two (E-J) independent experiments. Statistical analysis was performed by two-way ANOVA with Bonferroni’s multiple comparison test (M). Asterisks indicate significant differences (P < 0.05) between WT and Nlrp3–/–—infected groups, while in 5E asterisks indicate significant differences (P < 0.05) between WT and immune deficient-infected groups.