Therapeutic potential of phages in autoimmune liver diseases

Abstract

SummaryAutoimmune liver disease (ALD) poses a difficult medical challenge, as there is a significant number of patients in whom current therapy offers questionable or no benefit, yet its side effects may be serious, including the development of malignancy. Bacterial viruses (phages) have been recognized increasingly as immunomodulators contributing to immune homeostasis and curbing inflammation. Accumulating data suggest that phages may be useful in immunotherapy of ALD. Phages have been shown to down‐regulate the expression and/or production and activity of factors associated with hepatic injury [reactive oxygen species, Toll‐like receptor (TLR)‐4 activation, nuclear factor kappa B (NF‐κB) activation, proinflammatory and procoagulant activities of platelets] and up‐regulate the expression and/or production of factors demonstrated as playing a protective role [interleukin (IL)‐10, IL‐1 receptor antagonist].

Phage Therapy of Pneumonia Is Not Associated with an Overstimulation of the Inflammatory Response Compared to Antibiotic Treatment in Mice

“…With strong clinical implications, these interactions are observed, for example, during allograft rejection in solid organ transplantation (34) or during influenza virusassociated bacterial pneumonia (35). Data related to similar interactions regarding prokaryotic viruses (mainly phages) are scarce, but some authors have pointed out a potential immunomodulatory role of phages by themselves (36)(37)(38). As recently stressed by Krut et al, our ignorance is substantial regarding the immunological aspects of phage therapy, despite evidence that phages interact with the immune system on top of their synergistic activity with it (25).…”

Gut Microbiota and Liver Interaction through Immune System Cross-Talk: A Comprehensive Review at the Time of the SARS-CoV-2 Pandemic

“…In cases where immunosuppressive therapy does not offer any benefit, and the side effects are seriousleading to the development of malignancies, bacteriophage-based approaches have been considered. Bacteriophages have been increasingly recognized as immunomodulators contributing to immune homeostasis and curbing inflammation [122]. Phages have been shown to down-regulate the expression and/or production and activity of factors associated with hepatic injury (e.g., reactive oxygen species, TLR-4 and NF-kB activation, pro-inflammatory and pro-coagulant activities of platelets) and up-regulate the expression and/or production of protective factors (e.g., IL-10, IL-1 receptor antagonist) [121].…”

Phage Therapy: What Have We Learned?

“…Phages have been shown to mediate anti-inflammatory and immunomodulating properties [ 279 ]; therefore, such phenomena may be relevant for the maintenance of immunological homeostasis. Consequently, we recently hypothesized that phage therapy may be considered for treating disorders such as inflammatory bowel disease, autoimmune hepatitis, allergy, as well as some viral infections [ 280 , 281 , 282 , 283 ]. Evidently, this requires further work and confirmation by relevant clinical trials.…”