Paired ATAC- and RNA-seq offer insight into the impact of HIV on alveolar macrophages: a pilot study

• Type of Material: Article
• Authors: Bashar S. Staitieh, Emory University; Xin Hu, Emory University; Samantha M. Yeligar, Emory University; Sara Auld, Emory University
• Language: English
• Date: 2023-09-15
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1038%2Fs41598-023-42644-7
• Title of Journal or Parent Work: Scientific Reports
• Volume: 13
• Start Page: 15276
• Grant/Funding Information: This work was supported in part by the National Institute of Allergy and Infectious Diseases (K23AI134182 to SCA), the Center for AIDS Research at Emory University (P30AI050409), the Emory/Georgia TB Research Advancement Center (P30AI168386), the National Institute on Alcohol Abuse and Alcoholism (K08AA024512 to BSS and R01AA026086 to SMY), the National Heart, Lung, and Blood Institute (R01HL166455 to XH) and institutional support of the Emory School of Medicine Doris Duke Charitable Foundation COVID-19 Fund to Retain Clinical Scientists and the Georgia CTSA NIH award number (UL1-TR002378), the Emory Integrated Computational Core (EICC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities. Additional support was provided by the National Center for Georgia Clinical & Translational Science Alliance of the National Institutes of Health under Award Number UL1TR002378.
• Keywords: Applied immunology; Mucosal immunology; Infectious diseases; Translational research
• Research Categories: Health Sciences, Immunology

Abstract

People with HIV remain at greater risk for both infectious and non-infectious pulmonary diseases even after antiretroviral therapy initiation and CD4 cell count recovery. These clinical risks reflect persistent HIV-mediated defects in innate and adaptive immunity, including in the alveolar macrophage, a key innate immune effector in the lungs. In this proof-of-concept pilot study, we leveraged paired RNA-seq and ATAC-seq analyses of human alveolar macrophages obtained with research bronchoscopy from people with and without HIV to highlight the potential for recent methodologic advances to generate novel hypotheses about biological pathways that may contribute to impaired pulmonary immune function in people with HIV. In addition to 35 genes that were differentially expressed in macrophages from people with HIV, gene set enrichment analysis identified six gene sets that were differentially regulated. ATAC-seq analysis revealed 115 genes that were differentially accessible for people with HIV. Data-driven integration of the findings from these complementary, high-throughput techniques using xMWAS identified distinct clusters involving lipoprotein lipase and inflammatory pathways. By bringing together transcriptional and epigenetic data, this analytic approach points to several mechanisms, including previously unreported pathways, that warrant further exploration as potential mediators of the increased risk of pulmonary disease in people with HIV.