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        Evaluation of host and bacterial gene modulation during Lawsonia intracellularis infection in immunocompetent C57BL/6 mouse model

        Kirthika, Perumalraja,Park, Sungwoo,Jawalagatti, Vijayakumar,Lee, John Hwa The Korean Society of Veterinary Science 2022 Journal of Veterinary Science Vol.23 No.3

        Background: Proliferative enteritis caused by Lawsonia intracellularis undermines the economic stability of the swine industry worldwide. The development of cost-effective animal models to study the pathophysiology of the disease will help develop strategies to counter this bacterium. Objectives: This study focused on establishing a model of gastrointestinal (GI) infection of L. intracellularis in C57BL/6 mice to evaluate the disease progression and lesions of proliferative enteropathy (PE) in murine GI tissue. Methods: We assessed the murine mucosal and cell-mediated immune responses generated in response to inoculation with L. intracellularis. Results: The mice developed characteristic lesions of the disease and shed L. intracellularis in the feces following oral inoculation with 5 × 10<sup>7</sup> bacteria. An increase in L. intracellularis 16s rRNA and groEL copies in the intestine of infected mice indicated intestinal dissemination of the bacteria. The C57BL/6 mice appeared capable of modulating humoral and cell-mediated immune responses to L. intracellularis infection. Notably, the expression of genes for the vitamin B12 receptor and for secreted and membrane-bound mucins were downregulated in L. intracellularis -infected mice. Furthermore, L. intracellularis colonization of the mouse intestine was confirmed by the immunohistochemistry and western blot analyses. Conclusions: This is the first study demonstrating the contributions of bacterial chaperonin and host nutrient genes to PE using an immunocompetent mouse model. This mouse infection model may serve as a platform from which to study L. intracellularis infection and develop potential vaccination and therapeutic strategies to treat PE.

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        Immunogenicity of a bacterial ghost delivered dengue virus serotype 2 envelope protein domain III followed by an intramuscular protein boosting strategy in mice model

        Gayeon Won,Irshad Ahmed Hajam,Perumalraja Kirthika,Eunha Kim,John Hwa Lee 한국예방수의학회 2022 예방수의학회지 Vol.46 No.3

        This study aimed to investigate whether bacterial ghosts (BGs), empty cell envelopes of a gram-negative bacterium, delivering envelope protein domain III (EDIII) of dengue virus (DENV) serotype 2 could induce protective immune responses against dengue infection. In this study, we constructed Salmonella Typhimurium BGs expressing and delivering EDIII (BG-EDIII) and evaluated these ghosts for their immunogenicity studies in C57BL/6 mice. Our results demonstrated that the mice vaccinated once orally with BG-EDIII followed by an intramuscular boosting with a recombinant EDIII protein elicited significantly higher humoral and cell-mediated immune responses compared to the BGs alone vaccinated group (p<0.001). Upon challenge with DENV2, significantly lower viral load and liver damage was observed in BG-EDIII vaccinated group than BGs alone control group (p<0.05). The outcomes of this study revealed the ability of BG- EDIII to stimulate immune response with no observable damage to the vital organs.

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