Toxoplasma gondii GRA9 Regulates the Activation of NLRP3 Inflammasome to Exert Anti-Septic Effects in Mice |
| |
| Authors: | Jae-Sung Kim Seok-Jun Mun Euni Cho Donggyu Kim Wooic Son Hye-In Jeon Hyo Keun Kim Kiseok Jang Chul-Su Yang |
| |
| Affiliation: | 1.Institute of Natural Science & Technology, Hanyang University, Ansan 15588, Korea; ;2.Department of Bionano Technology, Hanyang University, Seoul 04673, Korea; (S.-J.M.); (E.C.);3.Department of Molecular and Life Science, Hanyang University, Ansan 15588, Korea; (D.K.); (W.S.); (H.-I.J.); (H.K.K.);4.Department of Pathology, Hanyang University College of Medicine, Seoul 04673, Korea; |
| |
| Abstract: | Dense granule proteins (GRAs) are essential components in Toxoplasma gondii, which are suggested to be promising serodiagnostic markers in toxoplasmosis. In this study, we investigated the function of GRA9 in host response and the associated regulatory mechanism, which were unknown. We found that GRA9 interacts with NLR family pyrin domain containing 3 (NLRP3) involved in inflammation by forming the NLRP3 inflammasome. The C-terminal of GRA9 (GRA9C) is essential for GRA9–NLRP3 interaction by disrupting the NLRP3 inflammasome through blocking the binding of apoptotic speck-containing (ASC)-NLRP3. Notably, Q200 of GRA9C is essential for the interaction of NLRP3 and blocking the conjugation of ASC. Recombinant GRA9C (rGRA9C) showed an anti-inflammatory effect and the elimination of bacteria by converting M1 to M2 macrophages. In vivo, rGRA9C increased the anti-inflammatory and bactericidal effects and subsequent anti-septic activity in CLP- and E. coli- or P. aeruginosa-induced sepsis model mice by increasing M2 polarization. Taken together, our findings defined a role of T. gondii GRA9 associated with NLRP3 in host macrophages, suggesting its potential as a new candidate therapeutic agent for sepsis. |
| |
| Keywords: | Toxoplasma gondii GRA9 NLRP3 macrophages polarization sepsis |
|
|
