Infectious Tolerance as Seen With 2020 Vision: The Role of IL-35 and Extracellular Vesicles

• Type of Material: Article
• Authors: Jeremy A. Sullivan, University of Wisconsin; David P. AlAdra, University of Wisconsin; Brian Olson, Emory University; Douglas G. McNeel, University of Wisconsin; William J. Burlingham, University of Wisconsin
• Language: English
• Date: 2020-08-26
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Sullivan, AlAdra, Olson, McNeel and Burlingham.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fimmu.2020.01867
• Title of Journal or Parent Work: FRONTIERS IN IMMUNOLOGY
• Volume: 11
• Start Page: 1867
• End Page: 1867
• Grant/Funding Information: This work was supported by R01AI119140, and R21AI147157-01 (to WB), R03AI146688-01 (to JS), The Society for Surgery of the Alimentary Tract CareerDevelopment Award (to DA), and by R01CA219154 (to DM). DOD Idea Development Award W81XWH1910840 (to BO).
• Keywords: immunotherapy; Life Sciences & Biomedicine; INDUCTION; MATERNAL HLA ANTIGENS; UNRESPONSIVENESS; Immunology; TRANSPLANTATION; COLLAGEN TYPE-V; CD73; infectious tolerance; extracellular vesicle; ADENOSINE; exosomes; REGULATORY T-CELLS; GROWTH-FACTORS; Science & Technology; EXOSOMES; IL-35
• Research Categories: Health Sciences, Public Health; Health Sciences, Immunology

Abstract

Originally identified as lymphocyte regulation of fellow lymphocytes, our understanding of infectious tolerance has undergone significant evolutions in understanding since being proposed in the early 1970s by Gershon and Kondo and expanded upon by Herman Waldman two decades later. The evolution of our understanding of infectious tolerance has coincided with significant cellular and humoral discoveries. The early studies leading to the isolation and identification of Regulatory T cells (Tregs) and cytokines including TGFβ and IL-10 in the control of peripheral tolerance was a paradigm shift in our understanding of infectious tolerance. More recently, another potential, paradigm shift in our understanding of the “infectious” aspect of infectious tolerance was proposed, identifying extracellular vesicles (EVs) as a mechanism for propagating infectious tolerance. In this review, we will outline the history of infectious tolerance, focusing on a potential EV mechanism for infectious tolerance and a novel, EV-associated form for the cytokine IL-35, ideally suited to the task of propagating tolerance by “infecting” other lymphocytes.