Viral immune surveillance: Toward a TH17/TH9 gate to the central nervous system

Journal Name: 
Bioinformation.
Authors: 
Barkhordarian,A.
Thames,A.D.
Du,A.M.
Jan,A.L.
Nahcivan,M.
Nguyen,M.T.
Sama,N.
Chiappelli,F.
Abstract: 
Viral cellular immune surveillance is a dynamic and fluid system that is driven by finely regulated cellular processes including cytokines and other factors locally in the microenvironment and systemically throughout the body. It is questionable as to what extent the central nervous system (CNS) is an immune-privileged organ protected by the blood-brain barrier (BBB). Recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may alter the integrity of the blood-brain barrier, and lead to inflammation, swelling of the brain parenchyma and associated neurological syndromes. Here, we expand upon the recent "gateway theory", by which viral infection and other immune activation states may disrupt the specialized tight junctions of the BBB endothelium making it permeable to immune cells and factors. The model we outline here builds upon the proposition that this process may actually be initiated by cytokines of the IL-17 family, and recognizing the intimate balance between TH17 and TH9 cytokine profiles systemically. We argue that immune surveillance events, in response to viruses such as the Human Immunodeficiency Virus (HIV), cause a TH17/TH9 induced gateway through blood brain barrier, and thus lead to characteristic neuroimmune pathology. It is possible and even probable that the novel TH17/TH9 induced gateway, which we describe here, opens as a consequence of any state of immune activation and sustained chronic inflammation, whether associated with viral infection or any other cause of peripheral or central neuroinflammation. This view could lead to new, timely and critical patient-centered therapies for patients with neuroimmune pathologies across a variety of etiologies. ABBREVIATIONS:
2015
Volume: 
11
Pages: 
47-54
Keywords: 
blood, Brain, Central Nervous System, decision, Dentistry, electronic, etiology, factors, Family, Human, Infection, Lead, Medicine, pathology, patient, Patients, practice-based research, Psychiatry, Research, response, system, therapy