@article{15913528ac46430f9120ea9bfb1525ea,
title = "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.",
keywords = "HIV, SIV, immunosuppression, multiplexed imaging, single-cell biology, spatial multiomics, viral pathogenesis, viral reservoir, virus-host interactions",
author = "Sizun Jiang and Chan, {Chi Ngai} and Xavier Rovira-Clav{\'e} and Han Chen and Yunhao Bai and Bokai Zhu and Erin McCaffrey and Greenwald, {Noah F.} and Candace Liu and Barlow, {Graham L.} and Weirather, {Jason L.} and Oliveria, {John Paul} and Tsuguhisa Nakayama and Lee, {Ivan T.} and Matter, {Matthias S.} and Carlisle, {Anne E.} and Darci Philips and Gustavo Vazquez and Nilanjan Mukherjee and Kathleen Busman-Sahay and Michael Nekorchuk and Margaret Terry and Skyler Younger and Marc Bosse and Janos Demeter and Rodig, {Scott J.} and Alexandar Tzankov and Yury Goltsev and McIlwain, {David Robert} and Michael Angelo and Estes, {Jacob D.} and Nolan, {Garry P.}",
note = "Funding Information: The authors thank previous and current members of Ionpath Inc., including Matthew Newgren and Maciej Zerkowski, for their unwavering technical support. We thank Drs. Xiao-jun Ma and Bingqing Zhang from ACDBio for reagent support and discussions. We thank members of the Nolan, Estes, Angelo, and Jiang labs for helpful discussions. This study was supported by the Leukemia & Lymphoma Society Career Development Program (S.J.), Stanford Dean{\textquoteright}s Fellowship (S.J.), EMBO postdoctoral fellowship ALTF 300-2017 (X.R.-C.), Stanford Graduate Fellowship (B.Z.), NCI CA246880-01 (N.F.G.), Stanford Graduate Fellowship (N.F.G.), Canadian Institutes of Health Research Postdoctoral Fellowship (J.P.O.), Banting Postdoctoral Fellowship (J.P.O.), NIH R01AI149672 (S.J., G.P.N., and J.D.E.), Bill & Melinda Gates Foundation INV-002704 (S.J., G.P.N., and J.D.E.), OPP1113682 (G.P.N.), P51OD011092 (J.D.E.), COVID-19 Pilot Award (S.J., D.R.M., and G.P.N.), Fast Grant Funding for COVID-19 Science (G.P.N.), Botnar Research Centre for Child Health Emergency Response to COVID-19 grant (S.J., D.R.M., G.P.N., M.S.M., and A.T.), US Food and Drug Administration Medical Countermeasures Initiative contracts HHSF223201610018C and 75F40120C00176 (G.P.N.), Parker Institute for Cancer Immunotherapy (G.P.N.), and a Rachford and Carlota A. Harris Endowed Professorship (G.P.N.). This article reflects the views of the authors and should not be construed as representing the views or policies of the FDA, NIH, BMGF or other institutions that provided funding. Funding Information: The authors thank previous and current members of Ionpath Inc. including Matthew Newgren and Maciej Zerkowski, for their unwavering technical support. We thank Drs. Xiao-jun Ma and Bingqing Zhang from ACDBio for reagent support and discussions. We thank members of the Nolan, Estes, Angelo, and Jiang labs for helpful discussions. This study was supported by the Leukemia & Lymphoma Society Career Development Program (S.J.), Stanford Dean's Fellowship (S.J.), EMBO postdoctoral fellowship ALTF 300-2017 (X.R.-C.), Stanford Graduate Fellowship (B.Z.), NCI CA246880-01 (N.F.G.), Stanford Graduate Fellowship (N.F.G.), Canadian Institutes of Health Research Postdoctoral Fellowship (J.P.O.), Banting Postdoctoral Fellowship (J.P.O.), NIH R01AI149672 (S.J. G.P.N. and J.D.E.), Bill & Melinda Gates Foundation INV-002704 (S.J. G.P.N. and J.D.E.), OPP1113682 (G.P.N.), P51OD011092 (J.D.E.), COVID-19 Pilot Award (S.J. D.R.M. and G.P.N.), Fast Grant Funding for COVID-19 Science (G.P.N.), Botnar Research Centre for Child Health Emergency Response to COVID-19 grant (S.J. D.R.M. G.P.N. M.S.M. and A.T.), US Food and Drug Administration Medical Countermeasures Initiative contracts HHSF223201610018C and 75F40120C00176 (G.P.N.), Parker Institute for Cancer Immunotherapy (G.P.N.), and a Rachford and Carlota A. Harris Endowed Professorship (G.P.N.). This article reflects the views of the authors and should not be construed as representing the views or policies of the FDA, NIH, BMGF or other institutions that provided funding. Conceptualization, S.J. and J.D.E.; methodology, S.J. and J.D.E.; experimental investigation, S.J. C.N.C. X.R.-C. H.C. Y.B. B.Z. J.P.O. G.V. N.M. and J.D.E.; computational analysis, S.J. H.C. Y.B. C.L. and Y.G.; novel reagents and tools, E.M. N.F.G. G.L.B. J.L.W. T.N. I.T.L. M.S.M. A.E.C. D.P. K.B.-S. M.N. M.T. S.Y. M.B. J.D. S.J.R. and A.T.; visualization, S.J. H.C. and C.N.C.; writing, S.J. C.N.C. X.R.-C. J.D.E. and G.P.N.; funding acquisition, S.J. D.R.M. J.D.E. and G.P.N.; supervision: S.J. D.R.M. M.A. J.D.E. and G.P.N. All authors read and approved the final draft of the manuscript. S.J. C.N.C. and X.R.-C. contributed equally and have the right to list their name first in their CV. G.P.N. and M.A. are cofounders and stockholders of Ionpath Inc. which manufactures the instrument used in this manuscript. G.P.N. and Y.G. are cofounders and stockholders of Akoya Biosciences, Inc. and inventors on patent US9909167. S.J.R. is a Scientific Advisory Board member for KITE/Gilead and Immunitas Therapeutics. S.J. X.R.-C. Y.B. and G.P.N. are inventors on pending patent US17433542 related in part to this work. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = jun,
day = "14",
doi = "10.1016/j.immuni.2022.03.020",
language = "English (US)",
volume = "55",
pages = "1118--1134.e8",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "6",
}