Liver macrophage-associated inflammation correlates with SIV burden and is substantially reduced following cART

PLoS Pathogens
Bridget S FisherDonald L Sodora

Abstract

Liver disease is a leading contributor to morbidity and mortality during HIV infection, despite the use of combination antiretroviral therapy (cART). The precise mechanisms of liver disease during HIV infection are poorly understood partially due to the difficulty in obtaining human liver samples as well as the presence of confounding factors (e.g. hepatitis co-infection, alcohol use). Utilizing the simian immunodeficiency virus (SIV) macaque model, a controlled study was conducted to evaluate the factors associated with liver inflammation and the impact of cART. We observed an increase in hepatic macrophages during untreated SIV infection that was associated with a number of inflammatory and fibrosis mediators (TNFα, CCL3, TGFβ). Moreover, an upregulation in the macrophage chemoattractant factor CCL2 was detected in the livers of SIV-infected macaques that coincided with an increase in the number of activated CD16+ monocyte/macrophages and T cells expressing the cognate receptor CCR2. Expression of Mac387 on monocyte/macrophages further indicated that these cells recently migrated to the liver. The hepatic macrophage and T cell levels strongly correlated with liver SIV DNA levels, and were not associated with the levels of 16S...Continue Reading

References

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Citations

Jul 31, 2020·Viruses·Jay Lubow, Kathleen L Collins
Nov 28, 2018·World Journal of Gastroenterology : WJG·Murali GanesanNatalia A Osna
Jan 19, 2020·Journal of the International AIDS Society·Michael J PelusoUNKNOWN SEARCH010/RV254 Study Group
Nov 28, 2020·The Journal of Infectious Diseases·Andre J Jeyarajan, Raymond T Chung
Aug 7, 2018·Journal of Agricultural and Food Chemistry·Animesh Chandra RoyXiangzhen Shen

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Datasets Mentioned

BETA
GSE97676

Methods Mentioned

BETA
biopsies
PCR
flow cytometry
ELISA
GTPase
deubiquitination
ubiquitination
sedation
Assay
Feature Extractor

Software Mentioned

heapmap
limma bioconductor
Agilent feature extractor
limma
WGCNA
bioconductor
GraphPad
Prism
SNAPSHOT
NDP Viewer

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