The Phagosome–Lysosome Fusion Is the Target of a Purified Quillaja saponin Extract (PQSE) in Reducing Infection of Fish Macrophages by the Bacterial Pathogen Piscirickettsia salmonis

Abstract

Piscirickettsia salmonis, the etiological agent of Piscirickettsiosis, is a Gram-negative and facultative intracellular pathogen that has affected the Chilean salmon industry since 1989. The bacterium is highly aggressive and can survive and replicate within fish macrophages using the Dot/Icm secretion system to evade the host’s immune response and spread systemically. To date, no efficient control measures have been developed for this disease; therefore, the producers use large amounts of antibiotics to control this pathogen. In this frame, this work has focused on evaluating the use of saponins from Quillaja saponaria as a new alternative to control the Piscirickettsiosis. It has been previously reported that purified extract of Q. saponaria (PQSE) displays both antimicrobial activity against pathogenic bacteria and viruses and adjuvant properties. Our results show that PQSE does not present antimicrobial activity against P. salmonis, although it reduces P. salmonis infection in an in vitro model, promoting the phagosome–lysosome fusion. Additionally, we demonstrate that PQSE modulates the expression of IL-12 and IL-10 in infected cells, promoting the immune response against the pathogen and reducing the expression of pathogen virulence genes. These results together strongly argue for specific anti-invasion and anti-intracellular replication effects induced by the PQSE in macrophages.

Expression of immuno‐transcriptome response in red hybrid tilapia (Oreochromis sp.) hindgut following vaccination with feed‐based bivalent vaccine

“…According to the transcriptomic data, the phagosome and lysosome pathways were significantly enriched in the vaccinated fish hindgut ( p ≤ .05). Notably, the formation of a phagolysosome by the fusion of phagosome and lysosome demonstrated various bactericidal properties (Cortés et al., 2021). Lysosomes, a membrane‐bound cell organelle that contains digesting enzymes such as lysozyme, are essential for fish's non‐specific immunological response (Abdollahi et al., 2016).…”

In Vivo Efficacy of Purified Quillaja Saponin Extracts in Protecting against Piscirickettsia salmonis Infections in Atlantic Salmon (Salmo salar)

“…Although quillaja extracts have been used extensively as emulsifiers for foods and beverages, foaming agents, nematicides in agriculture and in many other applications [ 18 , 19 ], it is well known that some quillaja saponins are able to block viral and bacterial association with cells, as well as modulate intracellular processes. These biological effects lead to the induction of an innate and adaptive immune response, including cellular and humoral types [ 20 ]. High-grade quillaja extracts containing ≥90% w / w saponins (dry basis) can be employed as immunostimulant agents (vaccine adjuvants) in veterinary and human vaccine formulations [ 20 , 21 ], where they effectively modify the activities of antigen-presenting cells (macrophages and dendritic cells).…”

“…These biological effects lead to the induction of an innate and adaptive immune response, including cellular and humoral types [ 20 ]. High-grade quillaja extracts containing ≥90% w / w saponins (dry basis) can be employed as immunostimulant agents (vaccine adjuvants) in veterinary and human vaccine formulations [ 20 , 21 ], where they effectively modify the activities of antigen-presenting cells (macrophages and dendritic cells). It has been demonstrated that quillaja saponins, alone or incorporated into immune-stimulating complexes (ISCOMs), modulate immunity responses in different ways: by increasing antigen uptake in antigen-presenting cells (APC), by stimulating Th1 and Th2 immune responses to different antigens, and by inducing cytotoxic T lymphocytes (CTL) [ 22 ].…”

“…Specifically, quillaja extracts had the potential to reduce infections by 10- to 1000-fold according to in vitro assays [ 23 ]. In addition, purified quillaja saponin extract promotes phagosome–lysosome fusion and a balance in the expression of IL-12 and IL-10 in macrophage cell lines [ 20 ].…”