Host Immunity-Microbiota-Virus Interactions at the Intestinal Mucosal surface in Health and Disease
(2022) In Lund University, Faculty of Medicine Doctoral Dissertation Series- Abstract
- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/127e1cf1-a679-4119-a053-6b92854b66c2
- author
- Hamza, Kedir LU
- supervisor
-
- Katharina Lahl LU
- William Agace LU
- opponent
-
- Dr Ohnmacht, Caspar, München
- organization
- publishing date
- 2022-03-22
- type
- Thesis
- publication status
- published
- subject
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2022:57
- pages
- 61 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- GK-salen, BMC, Sölvegatan 19 i Lund. Join by Zoom: https://lu-se.zoom.us/j/68121436976
- defense date
- 2022-04-26 09:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-218-2
- language
- English
- LU publication?
- yes
- id
- 127e1cf1-a679-4119-a053-6b92854b66c2
- date added to LUP
- 2022-03-25 11:16:11
- date last changed
- 2022-04-01 08:48:15
@phdthesis{127e1cf1-a679-4119-a053-6b92854b66c2, abstract = {{The presence of viral immune triggers at the intestinal mucosa can have multiple<br/>global effects on intestinal integrity, including relative protection from<br/>subsequent inflammatory bowel disease. During the last century, the western<br/>world has achieved a remarkable success in preventing infectious diseases,<br/>which increased the general life expectancy dramatically. However, the<br/>incidence and prevalence of immune mediated diseases have increased<br/>immensely. Especially, the lack of exposure to microbial products during early<br/>development is considered to lead to the increase of allergy and autoimmune<br/>disease incidence.<br/>The overall aim of this thesis was to understand the host immunity-virusmicrobiota interaction at the intestinal mucosal surface in adults and neonates<br/>under homeostatic and inflammatory conditions. In the first paper, we showed<br/>that adult murine rotavirus (RV) infection did not induce significant long-lasting<br/>microbial community changes across the length of the intestine. Additionally,<br/>using acute Dextran Sodium Sulphate (DSS) colitis model, we demonstrated that<br/>prior infection with RV did not ameliorate inflammation of the colon. In the<br/>second paper, we demonstrated that the absence of maternal antibodies causes<br/>hyper-induction of IgA in neonates and this hyper-induction requires T cells help<br/>under homeostasis and RV infection conditions. We also discovered preferential<br/>IgA coating of colonic bacteria in neonates, as opposed to the stronger coating<br/>in the small intestine in adult mice, regardless of the antibody source.<br/>Additionally, we found that the increase in IgA+<br/> plasma cells during RV<br/>infection does not affect the level of IgA coating of bacteria in the neonatal gut.<br/>In the third paper, we showed that RV-induced expansion of antigen-specific<br/>CD8+<br/> T cells does not require signaling via TLR3, MyD88 or type I interferon<br/>receptor. In the fourth paper, we extended our studies to delineate when and how<br/>IgA against food antigens is induced and showed that induction of food-specific<br/>IgA in the gut requires adjuvant and T cells, but not TFH cells.<br/>Collectively, the work included in this thesis has broadened our understanding<br/>of intestinal homeostasis development and maintenance and of the complex<br/>interaction of host immunity, virus, and microbiota.}}, author = {{Hamza, Kedir}}, isbn = {{978-91-8021-218-2}}, issn = {{1652-8220}}, language = {{eng}}, month = {{03}}, number = {{2022:57}}, publisher = {{Lund University, Faculty of Medicine}}, school = {{Lund University}}, series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}}, title = {{Host Immunity-Microbiota-Virus Interactions at the Intestinal Mucosal surface in Health and Disease}}, url = {{https://lup.lub.lu.se/search/files/115807545/KedirHamza_PhDThesisSummary.pdf}}, year = {{2022}}, }