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Virus-Dependent Immune Conditioning of Tissue Microenvironments

View ORCID ProfileSizun Jiang, Chi Ngai Chan, Xavier Rovira-Clave, Han Chen, Yunhao Bai, Bokai Zhu, View ORCID ProfileErin McCaffrey, Noah F. Greenwald, Candace Liu, Graham L Barlow, Jason L. Weirather, John Paul Oliveria, Darci Philips, Nilanjan Mukherjee, Kathleen Busman-Sahay, Michael Nekorchuk, Margaret Terry, Skyler Younger, Marc Bosse, Janos Demeter, Yury Golstev, David Robert McIlwain, Michael Angelo, Jacob D. Estes, Garry P. Nolan
doi: https://doi.org/10.1101/2021.05.21.444548
Sizun Jiang
1Department of Pathology, Stanford University, Stanford, CA
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Chi Ngai Chan
2Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
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Xavier Rovira-Clave
1Department of Pathology, Stanford University, Stanford, CA
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Han Chen
1Department of Pathology, Stanford University, Stanford, CA
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Yunhao Bai
1Department of Pathology, Stanford University, Stanford, CA
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Bokai Zhu
1Department of Pathology, Stanford University, Stanford, CA
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Erin McCaffrey
1Department of Pathology, Stanford University, Stanford, CA
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Noah F. Greenwald
1Department of Pathology, Stanford University, Stanford, CA
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Candace Liu
1Department of Pathology, Stanford University, Stanford, CA
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Graham L Barlow
1Department of Pathology, Stanford University, Stanford, CA
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Jason L. Weirather
3Department of Data Science, Center of Immuno-Oncology, Dana-Faber Cancer Institute
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John Paul Oliveria
1Department of Pathology, Stanford University, Stanford, CA
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Darci Philips
1Department of Pathology, Stanford University, Stanford, CA
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Nilanjan Mukherjee
1Department of Pathology, Stanford University, Stanford, CA
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Kathleen Busman-Sahay
2Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
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Michael Nekorchuk
2Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
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Margaret Terry
2Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
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Skyler Younger
2Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
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Marc Bosse
1Department of Pathology, Stanford University, Stanford, CA
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Janos Demeter
1Department of Pathology, Stanford University, Stanford, CA
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Yury Golstev
1Department of Pathology, Stanford University, Stanford, CA
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David Robert McIlwain
1Department of Pathology, Stanford University, Stanford, CA
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Michael Angelo
1Department of Pathology, Stanford University, Stanford, CA
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Jacob D. Estes
2Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
4Division of Pathobiology & Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA
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  • For correspondence: gnolan@stanford.edu estesja@ohsu.edu
Garry P. Nolan
1Department of Pathology, Stanford University, Stanford, CA
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  • For correspondence: gnolan@stanford.edu estesja@ohsu.edu
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Abstract

A thorough understanding of complex spatial host-disease interactions in situ is necessary in order to develop effective preventative measures and therapeutic strategies. Here, we developed Protein And Nucleic acid IN situ Imaging (PANINI) and coupled it with Multiplexed Ion Beam Imaging (MIBI) to sensitively and simultaneously quantify DNA, RNA, and protein levels within the microenvironments of tissue compartments. The PANINI-MIBI approach was used to measure over 30 parameters simultaneously across large sections of archival lymphoid tissues from non-human primates that were healthy or infected with simian immunodeficiency virus (SIV), a model that accurately recapitulates human immunodeficiency virus infection (HIV). This enabled multiplexed dissection of cellular phenotypes, functional markers, viral DNA integration events, and viral RNA transcripts as resulting from viral infection. The results demonstrated immune coordination from an unexpected upregulation of IL10 in B cells in response to SIV infection that correlated with macrophage M2 polarization, thus conditioning a potential immunosuppressive environment that allows for viral production. This multiplexed imaging strategy also allowed characterization of the coordinated microenvironment around latently or actively infected cells to provide mechanistic insights into the process of viral latency. The spatial multi-modal framework presented here is applicable to deciphering tissue responses in other infectious diseases and tumor biology.

Competing Interest Statement

G.P.N. and M.A. are co-founders and have personal financial interests in the company IonPath, which manufactures the instrument used in this manuscript.

Footnotes

  • ↵# Senior Authors

  • The Key Resource Table has been added for this revision.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Virus-Dependent Immune Conditioning of Tissue Microenvironments
Sizun Jiang, Chi Ngai Chan, Xavier Rovira-Clave, Han Chen, Yunhao Bai, Bokai Zhu, Erin McCaffrey, Noah F. Greenwald, Candace Liu, Graham L Barlow, Jason L. Weirather, John Paul Oliveria, Darci Philips, Nilanjan Mukherjee, Kathleen Busman-Sahay, Michael Nekorchuk, Margaret Terry, Skyler Younger, Marc Bosse, Janos Demeter, Yury Golstev, David Robert McIlwain, Michael Angelo, Jacob D. Estes, Garry P. Nolan
bioRxiv 2021.05.21.444548; doi: https://doi.org/10.1101/2021.05.21.444548
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Virus-Dependent Immune Conditioning of Tissue Microenvironments
Sizun Jiang, Chi Ngai Chan, Xavier Rovira-Clave, Han Chen, Yunhao Bai, Bokai Zhu, Erin McCaffrey, Noah F. Greenwald, Candace Liu, Graham L Barlow, Jason L. Weirather, John Paul Oliveria, Darci Philips, Nilanjan Mukherjee, Kathleen Busman-Sahay, Michael Nekorchuk, Margaret Terry, Skyler Younger, Marc Bosse, Janos Demeter, Yury Golstev, David Robert McIlwain, Michael Angelo, Jacob D. Estes, Garry P. Nolan
bioRxiv 2021.05.21.444548; doi: https://doi.org/10.1101/2021.05.21.444548

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