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Commensal gut microbiota and the initiation of antiviral immunity in chickens infected with low pathogenic influenza virus subtype H9N2

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Title: Commensal gut microbiota and the initiation of antiviral immunity in chickens infected with low pathogenic influenza virus subtype H9N2
Author: Bekele-Yitbarek, Alexander
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Sharif, Shayan
Abstract: There is growing interest in understanding the relationship between viral infections and commensal microbiota of the host at various mucosal surfaces. It has been well established that commensal gut microbiota plays a major role in the development of the immune system, among other critical functions. However, very little is known about the role of commensal microbiota in viral infections in chickens. Therefore, in the four studies reported in this research, an attempt was made to understand the role of commensal gut microbiota in the initiation of antiviral responses against influenza virus subtype H9N2 infection in chickens. Findings from the initial study showed a shift in the composition of the gut microbiota after H9N2 virus infection, which did not recover to its original status while the virus shedding returned to levels of pre-infection. Furthermore, some bacterial populations, such as the phylum Proteobacteria, were enriched post-infection, whereas members of the order Actinomycetales, which are linked to the production of antimicrobial proteins, were suppressed. Next, a cocktail of antibiotics was used to induce dysbiosis of the gut microbiota. This study showed that antibiotic depletion significantly downregulated type I interferon (IFN) responses both in the upper respiratory and gastrointestinal tracts, followed by higher viral shedding from both sites. Next, the recovery of the gut microbiota using a cocktail of five lactobacilli probiotics or fecal microbial transplant (FMT) on innate responses, which included type I IFN and interleukin (IL)-22 expressions were used to study the effect on virus shedding and innate anti-viral responses. Both methods of recovery from dysbiosis showed recovery of type I IFN responses and a significant recovery in interleukin (IL)-22 expression, a cytokine that is highly involved in tissue regeneration. Recovery of the gut microbiota was associated with significant reduction in cloacal virus shedding. The last study was conducted to assess the role of commensal gut microbiota in response to vaccination with a whole inactivated influenza virus subtype H9N2. Administration of probiotics to undepleted chickens resulted in a significantly higher mean hemagglutination inhibition (HI) titre and virus-specific IgM and IgG titres compared to antibiotic treated chickens. Furthermore, chickens treated with probiotics and FMT post-antibiotic treatment showed a significantly higher mean HI titre and virus specific IgG titre compared to undepleted chickens treated with probiotics. Analysis of IFN- expression in splenocytes to assess recall responses showed a significantly lower expression in antibiotic depleted chickens compared to undepleted, and FMT reconstituted chickens. Overall, the results of this thesis showed that commensal gut microbiota plays a critical role in the initiation of innate and antibody-mediated immune responses to influenza virus subtype H9N2 virus infection and vaccination.
Date: 2019-01

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