Streptococcus suis serotype 2(SS2)is a zoonotic pathogen that can cause acute infection,such as septicemia in pigs and streptococcal toxic shock-like syndrome(STSLS)in humans,indicating that SS2 can evade innate immun...Streptococcus suis serotype 2(SS2)is a zoonotic pathogen that can cause acute infection,such as septicemia in pigs and streptococcal toxic shock-like syndrome(STSLS)in humans,indicating that SS2 can evade innate immunity.Macrophages perform essential antimicrobial functions in the innate immune system by engulfing and killing pathogens.Previously,a dna K mutant strain that showed impaired phagocytosis resistance ability was screened from the transposon mutant library of SS2,but the specific mechanism is unclear.In this study,we further demonstrated that DnaK was required for SS2 to be antiphagocytosed by macrophages and survive in adverse environments.A mouse challenge experiment indicated that DnaK promoted bacteremia and systemic dissemination of SS2,enhancing bacterial pathogenicity.Western blot and immunofluorescence results indicated that DnaK could be secreted by SS2 and was able to enter RAW264.7 macrophages.Then,the endocytic receptor LRP1 regulated by DnaK was identified through RNA sequencing(RNA-Seq).We found that DnaK decreased both the mRNA and protein levels of LRP1.Knockdown of the LRP1β-chain(LRP1β)significantly decreased the phagocytosis rate of the SS2 strain ZY05719,suggesting that LRP1 is a phagocytic receptor of SS2.Furthermore,inhibitor treatment assays revealed that DnaK decreased LRP1 protein levels through the transcription factor PPARγand the ubiquitin-proteasome system.In summary,DnaK contributes to the phagocytosis resistance of SS2 by decreasing LRP1 protein levels in macrophages,providing new insights into the antiphagocytosis mechanisms of SS2 and helping to understand its pathogenesis.展开更多
基金funded by the National Key Research and Development Program of China(2021YFD1800400)the National Natural Science Foundation of China(32373018)+2 种基金Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(23)1029)the Excellent Research Innovation Team in Universities in Anhui Province,China(2022AH010088)the Shennong Scholar Project of Anhui Agricultural University,China(rc392101)。
文摘Streptococcus suis serotype 2(SS2)is a zoonotic pathogen that can cause acute infection,such as septicemia in pigs and streptococcal toxic shock-like syndrome(STSLS)in humans,indicating that SS2 can evade innate immunity.Macrophages perform essential antimicrobial functions in the innate immune system by engulfing and killing pathogens.Previously,a dna K mutant strain that showed impaired phagocytosis resistance ability was screened from the transposon mutant library of SS2,but the specific mechanism is unclear.In this study,we further demonstrated that DnaK was required for SS2 to be antiphagocytosed by macrophages and survive in adverse environments.A mouse challenge experiment indicated that DnaK promoted bacteremia and systemic dissemination of SS2,enhancing bacterial pathogenicity.Western blot and immunofluorescence results indicated that DnaK could be secreted by SS2 and was able to enter RAW264.7 macrophages.Then,the endocytic receptor LRP1 regulated by DnaK was identified through RNA sequencing(RNA-Seq).We found that DnaK decreased both the mRNA and protein levels of LRP1.Knockdown of the LRP1β-chain(LRP1β)significantly decreased the phagocytosis rate of the SS2 strain ZY05719,suggesting that LRP1 is a phagocytic receptor of SS2.Furthermore,inhibitor treatment assays revealed that DnaK decreased LRP1 protein levels through the transcription factor PPARγand the ubiquitin-proteasome system.In summary,DnaK contributes to the phagocytosis resistance of SS2 by decreasing LRP1 protein levels in macrophages,providing new insights into the antiphagocytosis mechanisms of SS2 and helping to understand its pathogenesis.
