A proposed role of human defensins in Helicobacter pylori-related neurodegenerative disorders.
Cationic host defence peptides (CHDPs), also known as antimicrobial peptides (AMPs), are essential components of the innate immunity with antimicrobial and pleiotropic immunomodulatory properties. In mammals the two major families of CHDPs are defensins and cathelicidins that comprise an arsenal of innate regulators of principal importance in the host tissues. Research in the last decade has demonstrated that defensins are crucial effectors of both innate and adaptive immunity. Defensins can modulate immune responses, either by stimulation or suppression, thereby controlling inflammatory processes and infections. Currently only few data, mostly hypothetical, focus on the role of defensins in central nervous system (CNS) physiopathology and neurodegeneration. Defensins may function as an initial line of defense within the CNS either as an antimicrobial, immunomodulator, or both. A dysregulation of brain expression of specific defensins might either exacerbate or ameliorate the inflammatory response within the CNS depending upon which extracellular conditions predominate. It is proposed that reduction or abnormal elevation of AMP expression by cerebral microglia, astrocytes or choroid plexus epithelium might contribute to loss of AMP-induced regulation of immune responses, thereby promoting neuronal cell injury and death observed in Alzheimer's disease and possibly in other neurodegenerative disorders. Nevertheless, whether certain AMPs play a crucial role in the onset or promotion of the neuroinflammatory process and neurodegeneration is currently unknown, thereby emphasizing the necessity of further investigation into the regulatory mechanisms that control innate and adaptive immunity within the brain. Recent data indicate that Helicobacter pylori (H. pylori) induces defensins' release associated with chronic inflammatory tissue damage. However, it remains unclear whether and how H. pylori evades the attack by defensins. Moreover, recent evidence indicates that H. pylori infection might contribute to the pathogenesis of neurodegenerative diseases, by releasing several inflammatory mediators that could induce blood-brain barrier breakdown, thereby being involved in the pathogenesis of neurodegeneration. However, currently there are no data regarding the potential impact of human defensins on H. pylori-related neurodegenerative disorders. We herein propose that human defensins might contribute to the pathophysiology of H. pylori-related neurodegenerative disorders by modulating variably innate and adaptive immune system responses. Better understanding of the mechanisms regarding human defensins' possible involvement in H. pylori-induced neurodegeneration might help develop novel therapeutic strategies against H. pylori-related neurodegenerative disorders.
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece. Electronic address: jannis@auth.gr.
Jannis
J
Kountouras
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Georgia
G
Deretzi
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Emmanouel
E
Gavalas
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Christos
C
Zavos
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Stergios A
SA
Polyzos
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Evangelos
E
Kazakos
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Evangelia
E
Giartza-Taxidou
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Elisabeth
E
Vardaka
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Constantinos
C
Kountouras
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Panagiotis
P
Katsinelos
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Marina
M
Boziki
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Olga
O
Giouleme
D023082:Defensins / Q000502:physiology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000382:microbiology* / Q000517:prevention & control
D023082:Defensins