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Combined protein and nucleic acid imaging reveals virus-dependent B cell and macrophage immunosuppression of tissue microenvironments.


ABSTRACT: Understanding the mechanisms of HIV tissue persistence necessitates the ability to visualize tissue microenvironments where infected cells reside; however, technological barriers limit our ability to dissect the cellular components of these HIV reservoirs. Here, we developed protein and nucleic acid in situ imaging (PANINI) to simultaneously quantify DNA, RNA, and protein levels within these tissue compartments. By coupling PANINI with multiplexed ion beam imaging (MIBI), we measured over 30 parameters simultaneously across archival lymphoid tissues from healthy or simian immunodeficiency virus (SIV)-infected nonhuman primates. PANINI enabled the spatial dissection of cellular phenotypes, functional markers, and viral events resulting from infection. SIV infection induced IL-10 expression in lymphoid B cells, which correlated with local macrophage M2 polarization. This highlights a potential viral mechanism for conditioning an immunosuppressive tissue environment for virion production. The spatial multimodal framework here can be extended to decipher tissue responses in other infectious diseases and tumor biology.

SUBMITTER: Jiang S 

PROVIDER: S-EPMC9220319 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Combined protein and nucleic acid imaging reveals virus-dependent B cell and macrophage immunosuppression of tissue microenvironments.

Jiang Sizun S   Chan Chi Ngai CN   Rovira-Clavé Xavier X   Chen Han H   Bai Yunhao Y   Zhu Bokai B   McCaffrey Erin E   Greenwald Noah F NF   Liu Candace C   Barlow Graham L GL   Weirather Jason L JL   Oliveria John Paul JP   Nakayama Tsuguhisa T   Lee Ivan T IT   Matter Matthias S MS   Carlisle Anne E AE   Philips Darci D   Vazquez Gustavo G   Mukherjee Nilanjan N   Busman-Sahay Kathleen K   Nekorchuk Michael M   Terry Margaret M   Younger Skyler S   Bosse Marc M   Demeter Janos J   Rodig Scott J SJ   Tzankov Alexandar A   Goltsev Yury Y   McIlwain David Robert DR   Angelo Michael M   Estes Jacob D JD   Nolan Garry P GP  

Immunity 20220420 6


Understanding the mechanisms of HIV tissue persistence necessitates the ability to visualize tissue microenvironments where infected cells reside; however, technological barriers limit our ability to dissect the cellular components of these HIV reservoirs. Here, we developed protein and nucleic acid in situ imaging (PANINI) to simultaneously quantify DNA, RNA, and protein levels within these tissue compartments. By coupling PANINI with multiplexed ion beam imaging (MIBI), we measured over 30 par  ...[more]

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