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

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.
Competing Interests: Declaration of interests 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.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)