Cargando…
The TLR7/IRF-5 axis sensitizes memory CD4(+) T cells to Fas-mediated apoptosis during HIV-1 infection
HIV-1 infection is characterized by inflammation and a progressive decline in CD4(+) T cell count. Despite treatment with antiretroviral therapy (ART), the majority of people living with HIV (PLWH) maintain residual levels of inflammation, a low degree of immune activation, and higher sensitivity to...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371351/ https://www.ncbi.nlm.nih.gov/pubmed/37227774 http://dx.doi.org/10.1172/jci.insight.167329 |
Sumario: | HIV-1 infection is characterized by inflammation and a progressive decline in CD4(+) T cell count. Despite treatment with antiretroviral therapy (ART), the majority of people living with HIV (PLWH) maintain residual levels of inflammation, a low degree of immune activation, and higher sensitivity to cell death in their memory CD4(+) T cell compartment. To date, the mechanisms responsible for this high sensitivity remain elusive. We have identified the transcription factor IRF-5 to be involved in impairing the maintenance of murine CD4(+) T cells during chronic infection. Here, we investigate whether IRF-5 also contributes to memory CD4(+) T cell loss during HIV-1 infection. We show that TLR7 and IRF-5 were upregulated in memory CD4(+) T cells from PLWH, when compared with naturally protected elite controllers and HIV(free) participants. TLR7 was upstream of IRF-5, promoting Caspase 8 expression in CD4(+) T cells from ART HIV-1(+) but not from HIV(free) donors. Interestingly, the TLR7/IRF-5 axis acted synergistically with the Fas/FasL pathway, suggesting that TLR7 and IRF-5 expression in ART HIV-1(+) memory CD4(+) T cells represents an imprint that predisposes cells to Fas-mediated apoptosis. This predisposition could be blocked using IRF-5 inhibitory peptides, suggesting IRF-5 blockade as a possible therapy to prevent memory CD4(+) T cell loss in PLWH. |
---|