CNS-targeted autoimmunity leads to increased influenza mortality in mice.

Autor:	Glenn JD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Smith MD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Xue P; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Chan-Li Y; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Collins S; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Calabresi PA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Horton MR; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Whartenby KA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 whartenby@jhmi.edu.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2017 Feb; Vol. 214 (2), pp. 297-307. Date of Electronic Publication: 2017 Jan 05.
DOI:	10.1084/jem.20160517
Abstrakt:	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. (© 2017 Glenn et al.)
Databáze:	MEDLINE
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