Press release written by M.Sc. Estêvão Brasiliense de Souza.
Bacteriophages have long been regarded as viruses that exclusively target bacteria, devoid of any capacity to infect or interact with animal cells. However, recent evidence disrupts this conventional understanding, suggesting that bacteriophages go beyond targeting bacteria and can directly engage with animal cells, impacting their intracellular mechanisms. Researchers from Universidade Federal de Santa Catarina contribute to this paradigm shift with a review that not only explores the effects of bacteriophages on human and animal cells but also highlights their potential as anti-inflammatory agents.
The study explores the unexpected capacity of how these viral entities, traditionally seen as solely antimicrobial agents, exhibit the ability to modulate immune responses in both in vitro and in vivo environments. The article highlights the properties of bacteriophages that position them as potential anti-inflammatory tools, showcasing a tangible reduction in pro-inflammatory cytokines, chemokines, and inflammation-associated genes following phage application.Notably, bacteriophages demonstrate significant potential in mitigating arthritis severity and curtailing transplant rejection in animal models.
For quite some time, the anti-inflammatory effects observed after the application of bacteriophages have been underestimated, often dismissed as indirect outcomes stemming from a decrease in bacterial numbers caused by phage activity. This oversight is attributed to the prevalent use of bacteriophages in models focused on antibacterial applications, obscuring the potential impact of phage particles on animal cells by themselves. While acknowledging the role of reducing bacterial load in inflammation mitigation, the article delves deeper into the idea that bacteriophages go beyond merely alleviating inflammation through bacterial load reduction or bacterial lipopolysaccharide sequestration. Instead, it highlights that bacteriophages play a direct role in interacting with immune cells, even in the absence of bacteria.
The study further explores both established and potential mechanisms underpinning the anti-inflammatory effects of bacteriophages, elucidating the intricate ways in which these bacteria-targeting viruses interact with animal cells. Potential explanations encompass the interference of phage proteins with cell receptors, recognition of phage genetic material by toll-like receptors, hindrance of pro-inflammatory agent binding, or even the active induction of an anti-inflammatory cell profile. The article underscores that these mechanisms may not universally exist in every phage strain, emphasizing the necessity to consider phage diversity when opting to utilize them as anti-inflammatory agents.
While unveiling encouraging advancements in the utilization of phages as anti-inflammatories, the article underscores the possibility of an opposing effect. Studies have reported instances of heightened pro-inflammatory signals following phage application. Contributing factors to this divergence encompass phage strain immunogenicity, dosage, exposure time, and the development of anti-phage adaptive immunity. Souza’s research underscores the importance of comprehending the variables in phage application and the specific characteristics of each virus. This understanding is deemed essential for elucidating the precise immunoreactivity of bacteriophages and optimizing their therapeutic potential as anti-inflammatory agents.
In summary, the article acknowledges the potential of bacteriophages as versatile immunomodulatory tools, presenting an economically viable and highly adaptable option for clinical applications. Despite existing challenges, the article envisions a future where bacteriophages emerge as promising anti-inflammatory therapeutics, introducing a novel approach to address various animal and human diseases. The uncharted territory of phage pharmacology and the absence of a consensus on administration methods are recognized as hurdles deserving of further investigation. The review advocates for future exploration through clinical trials to assess the use of bacteriophages as potential anti-inflammatory agents, aiming to redefine their role beyond being merely antibacterial viruses.