Bacterial DNA(bacDNA) is frequently found in serum of patient with ulcerative colitis(UC) and Crohn's disease, even blood bacterial culture is negative. How bacDNA evades immune elimination and is translocated int...Bacterial DNA(bacDNA) is frequently found in serum of patient with ulcerative colitis(UC) and Crohn's disease, even blood bacterial culture is negative. How bacDNA evades immune elimination and is translocated into blood remain unclear. Here, we showed that bacDNA avoids elimination and disables bacteriakilling function of antimicrobial peptide LL-37(Cramp in mice) by forming complex with LL-37, which is inducible after culture with bacteria or bacterial products. Elevated LL-37-bacDNA complex was found in plasma and lesions of patients with UC. LL-37-bacDNA promoted inflammation by inducing Th1, Th2 and Th17 differentiation and activating toll-like receptor-9(TLR9). The complex also increased paracellular permeability, which possibly combines its inflammatory effects to promote local damage and bacDNA translocation into blood. Cramp-bacDNA aggravated mouse colitis severity while interference with the complex ameliorated the disease. The study identifies that inflammatogenic bacDNA utilizes LL-37 as a vehicle for blood translocation and to evade immune elimination. Additionally, bacteria may make a milieu by releasing bacDNA to utilize and resist host antimicrobial peptides as a ‘trojan horse'.展开更多
Dear editor,To date,a number of clinically approved drugs have been evaluated for potential to treat coronavirus disease 2019(COVID-19),such as lopinavir/ritonavir,hydroxychloroquine,cobicistat,and darunavir.Some of t...Dear editor,To date,a number of clinically approved drugs have been evaluated for potential to treat coronavirus disease 2019(COVID-19),such as lopinavir/ritonavir,hydroxychloroquine,cobicistat,and darunavir.Some of these drugs have been proven to be effective in vitro;however,clinical trials showed that none of these compounds led to a significant improvement in symptoms or length of hospitalization.Thus,it is essential and more reliable to start from a defined target to ide ntify can didate drugs.展开更多
基金supported by the National Natural Science Foundation of China(21761142002 and 81770464)Ministry of Science and Technology of the People’s Republic of China(2018ZX09301043-003)+2 种基金Chinese Academy of Science(QYZDJSSW-SMC012,SAJC201606the West Light Foundation and Youth Innovation Promotion Association(2017432))Yunnan Provincial Science and Technology Department(2017FB038,2015BC005)
文摘Bacterial DNA(bacDNA) is frequently found in serum of patient with ulcerative colitis(UC) and Crohn's disease, even blood bacterial culture is negative. How bacDNA evades immune elimination and is translocated into blood remain unclear. Here, we showed that bacDNA avoids elimination and disables bacteriakilling function of antimicrobial peptide LL-37(Cramp in mice) by forming complex with LL-37, which is inducible after culture with bacteria or bacterial products. Elevated LL-37-bacDNA complex was found in plasma and lesions of patients with UC. LL-37-bacDNA promoted inflammation by inducing Th1, Th2 and Th17 differentiation and activating toll-like receptor-9(TLR9). The complex also increased paracellular permeability, which possibly combines its inflammatory effects to promote local damage and bacDNA translocation into blood. Cramp-bacDNA aggravated mouse colitis severity while interference with the complex ameliorated the disease. The study identifies that inflammatogenic bacDNA utilizes LL-37 as a vehicle for blood translocation and to evade immune elimination. Additionally, bacteria may make a milieu by releasing bacDNA to utilize and resist host antimicrobial peptides as a ‘trojan horse'.
基金supported by grants from the Emergency Project of West China Hospital(number HX-2019-nCoV-025)the Program from Chongqing Education Commission(number KYYJ202010).
文摘Dear editor,To date,a number of clinically approved drugs have been evaluated for potential to treat coronavirus disease 2019(COVID-19),such as lopinavir/ritonavir,hydroxychloroquine,cobicistat,and darunavir.Some of these drugs have been proven to be effective in vitro;however,clinical trials showed that none of these compounds led to a significant improvement in symptoms or length of hospitalization.Thus,it is essential and more reliable to start from a defined target to ide ntify can didate drugs.