Liver Bacterial Dysbiosis With Non-Tuberculosis Mycobacteria Occurs in SIV-Infected Macaques and Persists During Antiretroviral Therapy

Frontiers in Immunology

Jeremy Smedley¹  Nina Derby¹  Andrew T. Gustin²  Michael Gale²  Donald L. Sodora³  Nichole R. Klatt⁴  Bridget S. Fisher⁵  Katherine A. Fancher⁵  Cole Fisher⁵  Matthew P. Wood⁵  Benjamin J. Burwitz⁶ 

[1] Science University, Beaverton, OR, United States;Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA, United States;Department of Surgery, University of Minnesota, Minneapolis, MN, United States;;Oregon National Primate Research Center, Oregon Health &Seattle Children’s Research Institute, Center for Global Infectious Disease Research, Seattle, WA, United States;;Vaccine and Gene Therapy Institute, Oregon Health &

关键词: HIV/SIV;    microbiome;    liver;    16S rRNA gene;    neutrophils;   

DOI  :  10.3389/fimmu.2021.793842

来源: DOAJ

【 摘 要 】

Liver disease is a significant contributor to morbidity and mortality in HIV-infected individuals, even during successful viral suppression with combination antiretroviral therapy (cART). Similar to HIV infection, SIV infection of rhesus macaques is associated with gut microbiome dysbiosis and microbial translocation that can be detected systemically in the blood. As microbes leaving the intestines must first pass through the liver via the portal vein, we evaluated the livers of both SIV-infected (SIV+) and SIV-infected cART treated (SIV+cART) rhesus macaques for evidence of microbial changes compared to uninfected macaques. Dysbiosis was observed in both the SIV+ and SIV+cART macaques, encompassing changes in the relative abundance of several genera, including a reduction in the levels of Lactobacillus and Staphylococcus. Most strikingly, we found an increase in the relative abundance and absolute quantity of bacteria within the Mycobacterium genus in both SIV+ and SIV+cART macaques. Multi-gene sequencing identified a species of atypical mycobacteria similar to the opportunistic pathogen M. smegmatis. Phosphatidyl inositol lipoarabinomannan (PILAM) (a glycolipid cell wall component found in atypical mycobacteria) stimulation in primary human hepatocytes resulted in an upregulation of inflammatory transcriptional responses, including an increase in the chemokines associated with neutrophil recruitment (CXCL1, CXCL5, and CXCL6). These studies provide key insights into SIV associated changes in hepatic microbial composition and indicate a link between microbial components and immune cell recruitment in SIV+ and SIV+cART treated macaques.

【 授权许可】

Unknown