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

Sizun Jiang, Chi Ngai Chan, Xavier Rovira-Clavé, Han Chen, Yunhao Bai, Bokai Zhu, Erin McCaffrey, Noah F. Greenwald, Candace Liu, Graham L. Barlow, Jason L. Weirather, John Paul Oliveria, Tsuguhisa Nakayama, Ivan T. Lee, Matthias S. Matter, Anne E. Carlisle, Darci Philips, Gustavo Vazquez, Nilanjan Mukherjee, Kathleen Busman-SahayMichael Nekorchuk, Margaret Terry, Skyler Younger, Marc Bosse, Janos Demeter, Scott J. Rodig, Alexandar Tzankov, Yury Goltsev, David Robert McIlwain, Michael Angelo, Jacob D. Estes, Garry P. Nolan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1118-1134.e8
JournalImmunity
Volume55
Issue number6
DOIs
StatePublished - Jun 14 2022

Keywords

  • HIV
  • SIV
  • immunosuppression
  • multiplexed imaging
  • single-cell biology
  • spatial multiomics
  • viral pathogenesis
  • viral reservoir
  • virus-host interactions

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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