Abstract
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.
Original language | English (US) |
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Article number | 793842 |
Journal | Frontiers in immunology |
Volume | 12 |
DOIs | |
State | Published - Jan 10 2022 |
Bibliographical note
Funding Information:The following reagents were obtained through BEI Resources, NIAID, NIH: Mycobacterium smegmatis, purified Lipoarabinomannan (LAM), NR-14849, and Mycobacterium tuberculosis, Strain H37Rv, purified LAM, NR-14848.
Publisher Copyright:
Copyright © 2022 Fisher, Fancher, Gustin, Fisher, Wood, Gale, Burwitz, Smedley, Klatt, Derby and Sodora.
Keywords
- 16S rRNA gene
- HIV/SIV
- liver
- microbiome
- neutrophils
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural