Oral Administration of Lactococcus lactis Producing Interferon Type II, Enhances the Immune Response Against Bacterial Pathogens in Rainbow Trout

Abstract

Lactic acid bacteria are a powerful vehicle for releasing of cytokines and immunostimulant peptides at the gastrointestinal level after oral administration. However, its therapeutic application against pathogens that affect rainbow trout and Atlantic salmon has been little explored. Type II interferon in Atlantic salmon activates the antiviral response, protecting against viral infection, but its role against bacterial infection has not been tested in vivo. In this work, through the design of a recombinant lactic acid bacterium capable of producing Interferon gamma from Atlantic salmon, we explore its role against bacterial infection and the ability to stimulate systemic immune response after oral administration of the recombinant probiotic. Recombinant interferon was active in vitro, mainly stimulating IL-6 expression in SHK-1 cells. In vivo, oral administration of the recombinant probiotic produced an increase in IL-6, IFNγ and IL-12 in the spleen and kidney, in addition to stimulating the activity of lysozyme in serum. The challenge trials indicated that the administration of the IFNγ-producing probiotic doubled the survival in fish infected with F. psychrophilum. In conclusion, our results showed that the oral administration of lactic acid bacteria producing IFNγ managed to stimulate the immune response at a systemic level, conferring protection against pathogens, showing a biotechnological potential for its application in aquaculture.

Screening and activity of potential gastrointestinal probiotic lactic acid bacteria against Yersinia ruckeri O1b

“…Few studies have also documented the capacity of lactic acid bacterial members to protect cultured fish from bacterial pathogens. Santibañez et al (2021), for instance, reported that Lactococcus lactis protected Rainbow trout ( Oncorhynchus mykiss ) from Lactocossis . Similarly, Fečkaninová et al (2019) reported that lactic acid bacterial consortia ( Lactobacillus plantarum , Lactobacillus fermentum and Lactobacillus brevis ) had antagonistic activity towards salmonid pathogens including Aeromonas salmonicida subsp.…”

Importance of Probiotics in Fish Aquaculture: Towards the Identification and Design of Novel Probiotics

“…Recombinant probiotics have also been used to express proteins that stimulate the immune response in fish, such as cytokines [ 145 , 146 ] and chemokines [ 147 ], the intestinal barrier [ 148 ], or enzymes that disrupt chemical communication in pathogens [ 149 ]. In the case of the cytokines, L. lactis has been used to deliver Interferon I and II, conferring protection against IPNV and F. psychrophilum , respectively [ 145 , 146 ].…”

Radiation Impacts Microbiota Compositions That Activate Transforming Growth Factor-Beta Expression in the Small Intestine

“…The mechanisms underlying post-viral bacterial infections are based on multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system [85][86][87], and may be summarized as the disruption of commensal microbiota homeostasis [88]. Since the effects of probiotics inoculation have never been sufficiently reported, its stimulatory impact on cytokine release should be mentioned at this point [89] (Scheme 2). Dysbiosis in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial and fungal infection, were focused on the beneficial changes in the microbial compositions in this review [84,[90][91][92].…”

“…Other current clinical trials explored the effectiveness of Lactobacillus plantarum and L. coryniformis as dietary supplements, or Lactococcus lactis via nasal irrigation in the context of COVID-19 [92]. Besides the release of IFN-α [93], IFN-γ, IL-2, and IL-12 from lactic acid bacteria (LAB) [89,90], TNF-α upregulation through a wide range of Lactobacilli [92], reduced viral entry through Bacillus subtilis [94], the production of defensins due to Lactobacillus casei [92] and the inhibition of chemokine responses related to Bifidobacterium animalis were described [95]. Enhancing the proliferation of potentially pathogenic bacterial species was limited.…”

“…Probiotic supplements reduced a "cytokine storm" and proinflammatory cytokines such as IL-1β, IL-6, and TNF-α [91]. Nevertheless, the pathogenesis of viral infections of the respiratory tract included infections with Staphylococcus pneumonia, Staphylococcus aureus, Hemophilus influenzae [89,90], Streptococcus pneumoniae, and Moraxella catarrhalis. Urinary tract infection following secondary colonization with Hemophilus and Pseudomonas aeruginosa induced immune responses, such as CXCL8 (C-X-C motif chemokine ligand 8), CCL2 and interleukins (IL-6, IL-8, IL-10, IL-17A), granulocyte colony stimulating factor (G-CSF), mucus response, and epithelial cell death [84].…”