SERTAD1 initiates NLRP3-mediated inflammasome activation through restricting NLRP3 polyubiquitination.

We here demonstrate that SERTAD1 is an adaptor protein responsible for the regulation of lysine 63 (K63)-linked NLRP3 polyubiquitination by the Cullin1 E3 ubiquitin ligase upon inflammasome activation. SERTAD1 specifically binds to NLRP3 but not to other inflammasome sensors. This endogenous interaction increases after inflammasome activation, interfering with the interaction between NLRP3 and Cullin1. Interleukin (IL)-1ß and IL-18 secretion, as well as the cleavage of gasdermin D, are decreased in SERTAD1 knockout bone-marrow-derived macrophages, together with reduced formation of the NLRP3 inflammasome complex. Additionally, SERTAD1-deficient mice show attenuated severity of monosodium-uric-acid-induced peritonitis and experimental autoimmune encephalomyelitis. Analysis of public datasets indicates that expression of SERTAD1 mRNA is significantly increased in the patients of autoimmune diseases. Thus, our findings uncover a function of SERTAD1 that specifically reduces Cullin1-mediated NLRP3 polyubiquitination via direct binding to NLRP3, eventually acting as a crucial factor to regulate the initiation of NLRP3-mediated inflammasome activation.

Molecular Detection of Giardia intestinalis from Stray Dogs in Animal Shelters of Gyeongsangbuk-do (Province) and Daejeon, Korea.

Giardia is a major public health concern and considered as reemerging in industrialized countries. The present study investigated the prevalence of giardiosis in 202 sheltered dogs using PCR. The infection rate was 33.2% (67/202); Gyeongsangbuk-do and Daejeon showed 25.7% (39/152, P<0.0001) and 56% (28/50), respectively. The prevalence of infected female dogs (46.7%, P<0.001) was higher than in male dogs (21.8%). A higher prevalence (43.5%, P<0.0001) was observed in mixed breed dogs than purebred (14.1%). Although most of the fecal samples collected were from dogs of ≥1 year of age which showed only 27.4% positive rate, 61.8% (P<0.001) of the total samples collected from young animals (<1 year of age) were positive for G. intestinalis. A significantly higher prevalence in symptomatic dogs (60.8%, P<0.0001) was observed than in asymptomatic dogs (23.8%). Furthermore, the analysis of nucleotide sequences of the samples revealed that G. intestinalis Assemblages A and C were found in the feces of dogs from Gyeongsangbuk-do and Daejeon. Since G. intestinalis Assemblage A has been known to infect humans, our results suggest that dogs can act as an important reservoir of giardiosis in Korea. Hence, hygienic management should be given to prevent possible transmission to humans.

Seroprevalence of Encephalitozoon cuniculi in pet rabbits in Korea.

Encephalitozoon cuniculi is a microsporidian parasite commonly found in rabbits that can infect humans, causing encephalitozoonosis. The prevalence of encephalitozoonosis is not well documented, even when many clinics suspect pet rabbits as being highly infected. This study investigated the seropositivity of E. cuniculi using ELISA. The examination of 186 rabbits using ELISA showed that 22.6% (42/186) were seropositive against E. cuniculi. In analysis with healthy status, all 42 seropositive sera were collected from clinically normal rabbits. Moreover, the gender and age of pet rabbits did not have anysignificant effect on E. cuniculi infection. To the best of our knowledge, this is the first report to describe the seroprevalence of E. cuniculi in pet rabbits and suggests that pet rabbits could act as an important reservoir of encephalitozoonosis for both pet animals and humans in Korea.