IL-2 induces robust inflammatory responses in the lung that synergize with influenza virus to exacerbate immunopathology
-
1
University of Massachusetts Medical School, Pathology, United States
Interleukin-2 (IL-2) is an important T cell growth factor central for the homeostasis and function of regulatory CD4 T cells (Tregs) that maintain tolerance and dampen inflammation. Systemic administration of IL-2 expands Tregs and improves autoimmune disease and transplant acceptance. On the other hand, IL-2 expands CD8 T and NK cells and cancer therapies aimed at improving the function of these subsets through administration of IL-2 are often complicated by severe side effects including systemic inflammatory cytokine (IFN-γ, TNF, and IL-5) production, eosinophelia, and death. To better understand the pro versus anti-inflammatory roles of IL-2 in vivo, we administered soluble cytokine, or IL-2 complexed with antibodies that target its delivery to specific cell types to unmanipulated mice and analyzed protein expression of over 40 inflammatory cytokines and chemokines. IL-2 up-regulates a remarkably broad array of these molecules, unexpectedly, even when targeted to Tregs. The IL-2 driven inflammation is as dramatic in lungs as it is systemically, and multiple T cell subsets, NK cells, and neutrophils, but not eosinophils, are involved in the inflammatory response. We next assessed whether IL-2 driven pulmonary inflammation is beneficial or detrimental during respiratory influenza A virus (IAV) infection as it is unclear whether concurrent infections exacerbate complications that arise during IL-2 therapy. IL-2 and virus synergized to markedly enhance inflammation that correlates with lower IAV titers, but morbidity was also strikingly increased. Our findings highlight the need to better understand the regulation of inflammation during pathogen infection and have implications for improving IL-2 based therapies.
Acknowledgements
This work was supported by NIH grants AI-45630 and NS-061014
Keywords:
Interleukin-2,
Inflammation Mediators,
Influenza A Virus, H1N1 Subtype,
Lung,
T regulatory cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Strutt
TM,
McKinstry
KK and
Swain
SL
(2013). IL-2 induces robust inflammatory responses in the lung that synergize with influenza virus to exacerbate immunopathology.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01205
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
12 Sep 2013;
Published Online:
19 Sep 2013.
*
Correspondence:
Dr. Tara M Strutt, University of Massachusetts Medical School, Pathology, Worcester, MA, 01605, United States, tara.strutt@ucf.edu