CNS-targeted autoimmunity leads to increased influenza mortality in mice

Justin D. Glenn, Matthew D. Smith, Pei Xue, Yee Chan-Li, Samuel Collins, Peter A. Calabresi, Maureen R. Horton, Katharine A. Whartenby

Research output: Contribution to journalArticle

Abstract

The discovery that central nervous system (CNS)-targeted autoreactive T cells required a process of licensing in the lung revealed an unexpected relationship between these organs. The clinical and immunological significance of this finding is bidirectional in that it showed not only a mechanism by which T cells become pathogenic before entering the CNS, but also the potential for this process to influence lung immunity as well. Epidemiological studies have shown that people with multiple sclerosis (MS) suffer from increased morbidity and mortality from infectious diseases, independent of immunosuppressive therapies. Respiratory infections account for a large percentage of deaths of people with MS. In this study, to investigate the mechanisms responsible for this enhanced susceptibility, we established a comorbid model system in which mice with experimental autoimmune encephalomyelitis (EAE) were administered a sublethal dose of influenza. Whereas mice with either EAE alone or influenza alone survived, 70% of comorbid mice died as a result of uncontrolled viral replication. Immunological analyses revealed that the induction of EAE led to a surprising alteration of the lung milieu, converting an effective stimulatory influenza-reactive environment into a suppressive one. These results provide mechanistic information that may help to explain the unexpected immunological interactions.

LanguageEnglish (US)
Pages297-307
Number of pages11
JournalJournal of Experimental Medicine
Volume214
Issue number2
DOIs
StatePublished - 2017

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Autoimmune Experimental Encephalomyelitis
Autoimmunity
Human Influenza
Central Nervous System
Lung
Multiple Sclerosis
Mortality
T-Lymphocytes
Licensure
Immunosuppressive Agents
Respiratory Tract Infections
Communicable Diseases
Epidemiologic Studies
Immunity
Morbidity
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

CNS-targeted autoimmunity leads to increased influenza mortality in mice. / Glenn, Justin D.; Smith, Matthew D.; Xue, Pei; Chan-Li, Yee; Collins, Samuel; Calabresi, Peter A.; Horton, Maureen R.; Whartenby, Katharine A.

In: Journal of Experimental Medicine, Vol. 214, No. 2, 2017, p. 297-307.

Research output: Contribution to journalArticle

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