Nematode serine protease inhibitor SPI-I8 negatively regulates host NF-κB signalling by hijacking MKRN1-mediated polyubiquitination of RACK1.

ABSTRACT: Parasitic roundworms are remarkable for their ability to manipulate host immune systems and ameliorate inflammatory diseases. Although much is known about the nature of nematode effectors in immune modulation, little is known about the action mode of these molecules. Here, we report that a serine protease inhibitor SPI-I8 in the extracellular vesicles of blood-feeding nematodes like Ancylostoma ceylanicum, Haemonchus contortus and Nippostrongylus brasiliensis, effectively halts excessive inflammatory responses in vitro and in vivo. We demonstrate that H. contortus SPI-I8 promotes the role of a negative regulator of RACK1 and enhances the effects of RACK1 on tumor necrosis factor (TNF)-α-IκB kinases (IKKs)-nuclear factor kappa beta (NF-κB) axis in mammalian cells, by hijacking E3 ubiquitin

SUBMITTER: Wu F 

PROVIDER: S-EPMC11876351 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature