The Dual Role of Antimicrobial Peptides in Autoimmunity

Abstract

Autoimmune diseases (AiDs) are characterized by the destruction of host tissues by the host immune system. The etiology of AiDs is complex, with the implication of multiple genetic defects and various environmental factors (pathogens, antibiotic use, pollutants, stress, and diet). The interaction between these two compartments results in the rupture of tolerance against self-antigens and the unwanted activation of the immune system. Thanks to animal models, the immunopathology of many AiDs is well described, with the implication of both the innate and adaptive immune systems. This progress toward the understanding of AiDs led to several therapies tested in patients. However, the results from these clinical trials have not been satisfactory, from reversing the course of AiDs to preventing them. The need for a cure has prompted many investigators to explore alternative aspects in the immunopathology of these diseases. Among these new aspects, the role of antimicrobial host defense peptides (AMPs) is growing. Indeed, beyond their antimicrobial activity, AMPs are potent immunomodulatory molecules and consequently are implicated in the development of numerous AiDs. Importantly, according to the disease considered, AMPs appear to play a dual role in autoimmunity with either anti- or pro-inflammatory abilities. Here, we aimed to summarize the current knowledge about the role of AMPs in the development of AiDs and attempt to provide some hypotheses explaining their dual role. Definitely, a complete understanding of this aspect is mandatory before the design of AMP-based therapies against AiDs.

Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation

“…These advantageous properties should warrant a successful treatment of chronic infectious diseases and chronic inflammation as found in people affected by CF. Furthermore, recent studies have described a protective role of AMPs produced by nonimmune cells in preventing the development of autoimmune diseases [ 58 ]. Therefore, AMPs like Esc peptides represent attractive compounds for the generation of new therapeutics able to modulate and/or arrest inflammation in autoimmunity [ 58 ], thus limiting the progression of immune-related diseases [ 58 , 59 , 60 ].…”

Serum defensin levels in patients with systemic sclerosis

“…AMP levels have been studied in some inflammatory diseases such as rheumatoid arthritis, SLE, inflammatory bowel disease, psoriasis, atopic dermatitis and familial Mediterranean fever (FMF). These studies showed that AMPs expression were irregular in diseases such as systemic lupus erythematosus (SLE), psoriasis, rheumatoid arthritis (RA), type 1 diabetes (T1D), Sjögren's disease (SjS) and multiple sclerosis (MS) [10]. Hiroyuki Tamiya et al reported significantly higher defensin and cathelicidin levels in active SLE patients [18].…”

“…In patients with systemic lupus erythematosus (SLE), alpha defensin and beta-2 defensin levels were found elevated and related with disease activity [8,9]. There is not much literature on the potential role of AMPs in SjS; however, some studies suggest that cathelicidin and defensins may have a role in the pathophysiology of the disease [10]. The role of AMPs in pulmonary diseases have been shown in idiopathic pulmonary fibrosis, diffuse panbronchiolitis and pulmonary alveolar proteinosis.…”

Novel therapeutic interventions towards improved management of septic arthritis

“…Also, the immune cells recruited by AMPs may also, play a regulatory function in balancing the inflammatory process. Secondly, AMPs modulate the activation of macrophages and dendritic cells by interacting with specific Toll-like receptor (TLR) ligands and by perturbing their pathways thus preventing undue activation of macrophages and dendritic cells [ 97 – 99 ]. For example, LL-37 suppresses the TLR-2 and TLR-4 induced production of TNF-α, IL-1β, IL-8 [ 97 , 100 ].…”