Spatial characterization of immunosenescence within HIV infected lymph nodes 2718

Description Persistent HIV replication is hypothesized to induce chronic inflammation in antiretroviral therapy (ART)-suppressed people living with HIV (PLWH). Molecular and spatial characterization of this chronic inflammation within human lymph nodes from PLWH provide valuable information on the immunological microenvironment that limits viral eradication. This study investigated the underlying mechanisms of this inflammation within lymph nodes from PLWH using 10X Visium spatial transcriptomics and proteomics, analyzing ART-suppressed, viremic, and HIV- control samples. Following infection, a strong Type-I interferon response was observed in antigen presenting cells within lymph nodes from viremic individuals, potentially through the cGAS-STING pathway. This interferon signature, particularly within the myeloid and B cell populations, was alleviated following viral suppression with antiretroviral drugs; however, a proinflammatory signature remained in aviremic individuals. In HIV+ lymph nodes, pro-inflammatory T cells remained within T cell zones, while two distinct pro-inflammatory myeloid cell populations were identified within the afferent and efferent lymphatics. The CD4+ T cell signature from viremic lymph nodes indicated a decrease in ARP2/3 complex genes, a reported senescence regulator. Ongoing research is investigating the role of ARP2/3 in HIV-associated inflammation, aiming to understand its contribution to persistent immune activation both before and after ART initiation. Funding Sources Funded in part by NIH grants UM1AI126617, UM1AI164559, U01DA058527, R01CA260691, and R01DA052027.