Autoimmunity Increases Susceptibility to and Mortality from Sepsis

Isaac J. Jensen, Samantha N. Jensen, Patrick W. McGonagill, Thomas S. Griffith, Ashutosh K. Mangalam, Vladimir P. Badovinac

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

We recently demonstrated how sepsis influences the subsequent development of experimental autoimmune encephalomyelitis (EAE) presented a conceptual advance in understanding the postsepsis chronic immunoparalysis state. However, the reverse scenario (autoimmunity prior to sepsis) defines a high-risk patient population whose susceptibility to sepsis remains poorly defined. In this study, we present a retrospective analysis of University of Iowa Hospital and Clinics patients demonstrating increased sepsis prevalence among multiple sclerosis (MS), relative to non-MS, patients. To interrogate how autoimmune disease influences host susceptibility to sepsis, well-established murine models of MS and sepsis and EAE and cecal ligation and puncture, respectively, were used. EAE, relative to non-EAE, mice were highly susceptible to sepsis-induced mortality with elevated cytokine storms. These results were further recapitulated in LPS and Streptococcus pneumoniae sepsis models. This work highlights both the relevance of identifying highly susceptible patient populations and expands the growing body of literature that host immune status at the time of septic insult is a potent mortality determinant.

Original languageEnglish (US)
Pages (from-to)844-854
Number of pages11
JournalImmunoHorizons
Volume5
Issue number10
DOIs
StatePublished - Oct 29 2021

Bibliographical note

Funding Information:
Received for publication July 23, 2021. Accepted for publication October 1, 2021. Address correspondence and reprint requests to: Dr. Vladimir Badovinac, Interdisciplinary Graduate Program in Immunology, University of Iowa, 1023 ML, 25 S. Grand Avenue, Iowa City, IA 52242. E-mail address: vladimir-badovinac@uiowa.edu ORCIDs: 0000-0002-3107-3961 (I.J.J.); 0000-0002-7205-9859 (T.S.G.); 0000-0002-9926-2531 (A.K.M.); 0000-0003-3180-2439 (V.P.B.). 1I.J.J. and S.N.J. are cofirst authors. This work was supported by National Institutes of Health Grants 5R01AI114543 (to V.P.B.), 1R35GM134880 (to V.P.B.), R01GM115462 (to T.S.G.), 1R35GM140881 (to T.S.G.), 5R01AI137075 (to A.K.M.), T32AI007511 (to I.J.J.), T32AI007485 (to I.J.J.), T32AI007485 (to S.N.J.), and 1R01AI137075-S1 (to S.N.J.); Veterans Health Administration Merit Review Award I01BX001324 (to T.S.G.); and the University of Iowa Environmental Health Sciences Research Center through National Institute of Environmental Health Sciences/National Institutes of Health (NIH) Grant P30 ES005605 (to A.K.M.). TriNetX is supported by the Institute for Clinical and Translational Science at the University of Iowa. The Institute for Clinical and Translational Science at the University of Iowa is supported by NIH Clinical and Translational Science Awards (CTSA) Program Grant UL1TR002537. The CTSA program is led by the NIH’s National Center for Advancing Translational Sciences. This publication’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Abbreviations used in this article: BHI, brain heart infusion; CLP, cecal ligation and puncture; D5, day 5; D15, day 15; D25, day 25; EAE, experimental autoimmune encephalomyelitis; HIPAA, Health Insurance Portability and Accountability Act; ICD, International Classification of Diseases; MS, multiple sclerosis. This article is distributed under the terms of the CC BY 4.0 Unported license.

Funding Information:
This work was supported by National Institutes of Health Grants 5R01AI114543 (to V.P.B.), 1R35GM134880 (to V.P.B.), R01GM115462 (to T.S.G.), 1R35GM140881 (to T.S.G.), 5R01AI137075 (to A.K.M.), T32AI007511 (to I.J.J.), T32AI007485 (to I.J.J.), T32AI007485 (to S.N.J.), and 1R01AI137075-S1 (to S.N.J.); Veterans Health Administration Merit Review Award I01BX001324 (to T.S.G.); and the University of Iowa Environmental Health Sciences Research Center through National Institute of Environmental Health Sciences/National Institutes of Health (NIH) Grant P30 ES005605 (to A.K.M.). TriNetX is supported by the Institute for Clinical and Translational Science at the University of Iowa. The Institute for Clinical and Translational Science at the University of Iowa is supported by NIH Clinical and Translational Science Awards (CTSA) Program Grant UL1TR002537. The CTSA program is led by the NIHs National Center for Advancing Translational Sciences. This publication̕s c̕ontents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. We thank members of the authors̕ laboratories and the laboratory of Dr. Nitin J. Karandikar for technical assistance and helpful discussions.

Publisher Copyright:
Copyright © 2021 The Authors

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