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

Kedir Hamza

Research output: ThesisDoctoral Thesis (compilation)

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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
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.
Original languageEnglish
Awarding Institution
  • Department of Experimental Medical Science
  • Lahl, Katharina, Supervisor
  • Agace, William, Assistant supervisor
Award date2022 Apr 26
Place of PublicationLund
ISBN (Print)978-91-8021-218-2
Publication statusPublished - 2022 Mar 22

Bibliographical note

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

Subject classification (UKÄ)

  • Immunology in the medical area


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