Extended Data Figure 5: Lymphoid CD4 T cells express detectable levels of ASC and NLRP3 relative to blood-derived monocytes.
From: Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection
The bipartite adaptor protein ASC (PYCARD) plays a central role in the interaction between (NOD)-like receptor and caspase 1 in inflammasome complexes63. Lymphoid CD4 T cells are primed to mount such inflammatory responses, and constitutively express high levels of cytoplasmic pro-IL-1β, but also ASC and NLRP3, compared to blood-derived monocytes. CD4 T lymphocytes express constitutive levels of NLRP3. In contrast to lymphocytes, monocytes require stimulation with TLR ligands such as LPS to induce NLRP3 expression21. Thus, the release of intracellular 5′-ATP by pyroptotic CD4 T cells may provide a second inflammatory stimulus to induce activation of caspase 1 by the NLRP3 inflammasome in nearby CD4 T cells that are already primed as reflected by their high levels of ASC, NLRP3 and pro-IL-1β expression. Thus, pyroptosis activated initially by HIV may result in cascade of new rounds of pyroptosis in primed CD4 T cells by the repeated release of intracellular ATP in a virus-independent manner. Such an ‘auto-inflammation’ scenario could result in persistent rounds of pyroptosis, chronic inflammation and loss of CD4 T cells even when viral loads are reduced by antiretroviral therapy (ART).
