Influenza virus infection exacerbates experimental autoimmune encephalomyelitis disease by promoting type I T cells infiltration into central nervous system.
Multiple sclerosis starts with increased migration of auto-reactive lymphocytes across the blood-brain barrier, resulting in persistent neurodegeneration. Clinical and epidemiological studies indicated upper respiratory viral infections are associated with clinical exacerbation of multiple sclerosis. However, so far there is no any direct evidence to support it. Using the experimental autoimmune encephalomyelitis mice as the model for multiple sclerosis, we demonstrated that mice experienced with influenza virus infection were unable to recover from experimental autoimmune encephalomyelitis with a long-term exacerbation. The exacerbated disease was due to more type I T cells, such as CD45highCD4+CD44high, CD45highCD4+CCR5+, CD45highIFNγ+CD4+, MOG35-55-specific IFNγ+CD4+and influenza virus-specific IFNγ+CD4+T cells, infiltrating central nervous system in mice with prior influenza virus infection. Influenza virus infection created a notable inflammatory environment in lung and mediastinal lymph node after influenza virus inoculation, suggesting the lung may constitute an inflammatory niche in which auto-aggressive T cells gain the capacity to enter CNS. Indeed, the early stage of EAE disease was accompanied by increased CCR5+CD4+, CXCR3+CD4+T cell and MOG35-55specific CD4+T cells localized in the lung in influenza virus-infected mice. CCL5/CCR5 might mediate the infiltration of type I T cells into CNS during the disease development after influenza infection. Administration of CCR5 antagonist could significantly attenuate the exacerbated disease. Our study provided the evidence that the prior influenza virus infection may promote the type I T cells infiltration into the CNS, and subsequently cause a long-term exacerbation of experimental autoimmune encephalomyelitis.
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, China.
Qingyun
Q
Chen
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, China.
Yinping
Y
Liu
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, China.
Aizhen
A
Lu
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, China.
Ke
K
Ni
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, China.
Zheng
Z
Xiang
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, China.
Kun
K
Wen
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, China. Electronic address: wwtu@hku.hk.
Wenwei
W
Tu
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000150:complications*; D010446:Peptide Fragments / Q000276:immunology; D019713:Receptors, CCR5 / Q000819:agonists; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D018836:Inflammation Mediators; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019713:Receptors, CCR5; C445081:myelin oligodendrocyte glycoprotein (35-55)
EAE; Influenza; Lung; Spinal cord; Type I T cells