Bystander Effects and Profibrotic Interactions in Hepatic Stellate Cells during HIV and HCV Coinfection

CEVALLOS, CINTIA; JARMOLUK, PATRICIO; SVIERCZ, FRANCO; LÓPEZ, CINTHYA A. M.; FREIBERGER, ROSA N.; DELPINO, M. VICTORIA; QUARLERI, JORGE

Journal of Immunology Research

Journal of Immunology Research

Año: 2024 vol. 2024 p. 1 - 14

2314-8861

This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up toactively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5).LX-2 cells’ susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-freevirus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed celldeath, ROS imbalance, cytokines (IL-6, TGF-β, and TNF-α), and extracellular matrix components (collagen, α-SMA, and MMP-9).The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes.Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidativestress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redoximbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cellsexhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This studyhighlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress,profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors.These insights offer valuable potential therapies for coinfected individuals.