Host Immunity-Microbiota-Virus Interactions at the Intestinal Mucosal surface in Health and Disease

Kedir Hamza

    Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

    193 Nedladdningar (Pure)

    Sammanfattning

    The presence of viral immune triggers at the intestinal mucosa can have multiple
    global effects on intestinal integrity, including relative protection from
    subsequent inflammatory bowel disease. During the last century, the western
    world has achieved a remarkable success in preventing infectious diseases,
    which increased the general life expectancy dramatically. However, the
    incidence and prevalence of immune mediated diseases have increased
    immensely. Especially, the lack of exposure to microbial products during early
    development is considered to lead to the increase of allergy and autoimmune
    disease incidence.
    The overall aim of this thesis was to understand the host immunity-virusmicrobiota interaction at the intestinal mucosal surface in adults and neonates
    under homeostatic and inflammatory conditions. In the first paper, we showed
    that adult murine rotavirus (RV) infection did not induce significant long-lasting
    microbial community changes across the length of the intestine. Additionally,
    using acute Dextran Sodium Sulphate (DSS) colitis model, we demonstrated that
    prior infection with RV did not ameliorate inflammation of the colon. In the
    second paper, we demonstrated that the absence of maternal antibodies causes
    hyper-induction of IgA in neonates and this hyper-induction requires T cells help
    under homeostasis and RV infection conditions. We also discovered preferential
    IgA coating of colonic bacteria in neonates, as opposed to the stronger coating
    in the small intestine in adult mice, regardless of the antibody source.
    Additionally, we found that the increase in IgA+
    plasma cells during RV
    infection does not affect the level of IgA coating of bacteria in the neonatal gut.
    In the third paper, we showed that RV-induced expansion of antigen-specific
    CD8+
    T cells does not require signaling via TLR3, MyD88 or type I interferon
    receptor. In the fourth paper, we extended our studies to delineate when and how
    IgA against food antigens is induced and showed that induction of food-specific
    IgA in the gut requires adjuvant and T cells, but not TFH cells.
    Collectively, the work included in this thesis has broadened our understanding
    of intestinal homeostasis development and maintenance and of the complex
    interaction of host immunity, virus, and microbiota.
    Originalspråkengelska
    KvalifikationDoktor
    Tilldelande institution
    • Institutionen för experimentell medicinsk vetenskap
    Handledare
    • Lahl, Katharina, handledare
    • Agace, William, Biträdande handledare
    Tilldelningsdatum2022 apr. 26
    UtgivningsortLund
    Förlag
    ISBN (tryckt)978-91-8021-218-2
    StatusPublished - 2022 mars 22

    Bibliografisk information

    Defence details
    Date: 2022-04-26]
    Time: 09:00
    Place: GK-salen, BMC, Sölvegatan 19 i Lund. Join by Zoom: https://lu-se.zoom.us/j/68121436976
    External reviewer(s)
    Name: Ohnmacht, Caspar
    Title: Dr
    Affiliation: München

    Ämnesklassifikation (UKÄ)

    • Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi)

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