Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in...Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.展开更多
Increased microbial translocation and chronic immune activation are two critical problems for people living with HIV(PLWH)in the antiretroviral therapy(ART)era.Compared with numerous studies on bacterial microbiomic c...Increased microbial translocation and chronic immune activation are two critical problems for people living with HIV(PLWH)in the antiretroviral therapy(ART)era.Compared with numerous studies on bacterial microbiomic communities,there are only a limited number of studies focusing on fungal microbiomic composition and products in PLWH.This study protocol is used to evaluate the changes in bacterial and fungal microbiome populations induced by terbinafine treatment,which is an antifungal agent widely used amongst PLWH.Twenty-two PLWH on a stable ART regimen for more than six months,who require treatment for onychomycosis,will be recruited.The participants will be followed-up for a 12-week treatment period(oral terbinafine 250mg daily)and another 12-weeks of terbinafine discontinuation.Plasma and fecal samples will be collected before and after terbinafine treatment,and for 12weeks after the discontinuation of terbinafine.Plasma gut injury and microbial translocation biomarker assays,in addition to testing for gut microbiome composition,will be undertaken.With this pilot study,we will perform formal sample size calculations and test study feasibility for a possible full-scale study.展开更多
The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopo...The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.展开更多
AIM： In order to characterize the qualitative and quantitative microorganisms in different sites of the lower digestive tract （LDT） in healthy volunteers, a specific technique was developed for collecting mucous of...AIM： In order to characterize the qualitative and quantitative microorganisms in different sites of the lower digestive tract （LDT） in healthy volunteers, a specific technique was developed for collecting mucous of the distal ileum, colon and rectum. METHODS： A polyethylene tube was designed to go through the colonoscope channel with a No. 8 French tube. In order to avoid internal contamination, the distal extremity was protected with a membrane of microfilm after being sterilized in ethilene oxid. To facilitate the aspiration of a precise volume, its interior was coated with silicone. One hundred rnicrolliter （0.1 mL） sample of mucous was collected and transferred into an Eppenddorff tube containing nine hundred rnicrolliter （0.9mL） of VMGA-3 （viable medium of Goteborg）. This procedure was repeated at each site of the LDT with a new sterilized catheter. RESULTS： All sites revealed the ＂non pathogenic＂ anaerobic bacteria Veillonella sp （average 10s colony forming units/mL-CFU/mL）, allowing to conclude an environment of low oxidation-reduction potential （redox） in the LDT. It was also characterized the presence of Klebisiella sp with significant statistical predominance （SSP） in the ileum. Enterobacter sp was found with SSP in the sigrnoid colon, Bacteroides sp non-pigmented （npg） and Ecoli with SSP in the sigrnoid colon and rectum, Enterococcus sp and Lactobacillus sp with SSP in the rectum, all in a mean concentration of 10s CFU/mL CONCLUSION： This procedure is feasible and efficient and can point out a similar distribution of the aerobic and anaerobic bacteria with the presence of biological markers of normal microbiota in the LDT.展开更多
基金partly supported by grants from the National Natural Science Foundation of China(U1802284 81471620,81671627,81771770,81571606)+1 种基金13th Five-Year Key Scientific and Technological Program of China(2017ZX10304402-002-004,2017ZX10202102-001-005,2018ZX10301101-002-003,2018ZX10301406-003)Knowledge Innovation Program of the Chinese Academy of Sciences(ZDRW-ZS-2016-4)
文摘Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.
基金This work was supported by the Joint Medical Research Project(2020GDRC010)of Chongqing Science&Technology Bureau and Chongqing Health Commission,the Research Project of Chinese Federation of Public Health foundation(GWLM202024)the Youth Scientific Research and Innovation Fund Project of Chongqing Public Health Medical Center(2019QNKYXM02).
文摘Increased microbial translocation and chronic immune activation are two critical problems for people living with HIV(PLWH)in the antiretroviral therapy(ART)era.Compared with numerous studies on bacterial microbiomic communities,there are only a limited number of studies focusing on fungal microbiomic composition and products in PLWH.This study protocol is used to evaluate the changes in bacterial and fungal microbiome populations induced by terbinafine treatment,which is an antifungal agent widely used amongst PLWH.Twenty-two PLWH on a stable ART regimen for more than six months,who require treatment for onychomycosis,will be recruited.The participants will be followed-up for a 12-week treatment period(oral terbinafine 250mg daily)and another 12-weeks of terbinafine discontinuation.Plasma and fecal samples will be collected before and after terbinafine treatment,and for 12weeks after the discontinuation of terbinafine.Plasma gut injury and microbial translocation biomarker assays,in addition to testing for gut microbiome composition,will be undertaken.With this pilot study,we will perform formal sample size calculations and test study feasibility for a possible full-scale study.
文摘The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.
文摘AIM： In order to characterize the qualitative and quantitative microorganisms in different sites of the lower digestive tract （LDT） in healthy volunteers, a specific technique was developed for collecting mucous of the distal ileum, colon and rectum. METHODS： A polyethylene tube was designed to go through the colonoscope channel with a No. 8 French tube. In order to avoid internal contamination, the distal extremity was protected with a membrane of microfilm after being sterilized in ethilene oxid. To facilitate the aspiration of a precise volume, its interior was coated with silicone. One hundred rnicrolliter （0.1 mL） sample of mucous was collected and transferred into an Eppenddorff tube containing nine hundred rnicrolliter （0.9mL） of VMGA-3 （viable medium of Goteborg）. This procedure was repeated at each site of the LDT with a new sterilized catheter. RESULTS： All sites revealed the ＂non pathogenic＂ anaerobic bacteria Veillonella sp （average 10s colony forming units/mL-CFU/mL）, allowing to conclude an environment of low oxidation-reduction potential （redox） in the LDT. It was also characterized the presence of Klebisiella sp with significant statistical predominance （SSP） in the ileum. Enterobacter sp was found with SSP in the sigrnoid colon, Bacteroides sp non-pigmented （npg） and Ecoli with SSP in the sigrnoid colon and rectum, Enterococcus sp and Lactobacillus sp with SSP in the rectum, all in a mean concentration of 10s CFU/mL CONCLUSION： This procedure is feasible and efficient and can point out a similar distribution of the aerobic and anaerobic bacteria with the presence of biological markers of normal microbiota in the LDT.
