Leiden University Scholarly Publications

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Costain, A.H. (2023)

Exploring host-immune-microbial interactions during intestinal schistosomiasis

Doctoral Thesis
During intestinal schistosomiasis, hundreds of parasite eggs transit across their mammalian host’s intestinal wall, triggering an exuberant immune response and considerable tissue damage. To limit host pathology and thereby promote their own survival, schistosomes produce a variety of immunomodulatory molecules that modify host immunity. Schistosomes may also gain assistance from the intestinal microbiota. This thesis dissects the involvement of parasite, host, and microbial factors in the instruction of schistosome-associated immune responses. Using mouse models of egg producing and non-egg producing schistosomiasis, this thesis provides a concise narrative of schistosome-associated immune profiles over time and across multiple tissue sites, and offers insight into the contribution of key cell types (Bregs, CD11c+ cells) and signalling networks (Type I interferons) in immune response instruction. Focusing on the intestine, this thesis describes the impact of schistosome egg...Show moreDuring intestinal schistosomiasis, hundreds of parasite eggs transit across their mammalian host’s intestinal wall, triggering an exuberant immune response and considerable tissue damage. To limit host pathology and thereby promote their own survival, schistosomes produce a variety of immunomodulatory molecules that modify host immunity. Schistosomes may also gain assistance from the intestinal microbiota. This thesis dissects the involvement of parasite, host, and microbial factors in the instruction of schistosome-associated immune responses. Using mouse models of egg producing and non-egg producing schistosomiasis, this thesis provides a concise narrative of schistosome-associated immune profiles over time and across multiple tissue sites, and offers insight into the contribution of key cell types (Bregs, CD11c+ cells) and signalling networks (Type I interferons) in immune response instruction. Focusing on the intestine, this thesis describes the impact of schistosome egg production on intestinal barrier integrity, microbiota structure and the colonic immune system. Finally, using germ-free mice and faecal transplants, this thesis provides evidence that the schistosome infection associated microbiota can influence the flavour of host Immunity. Together, these data elevate the mechanistic understanding of parasite-host-microbial relations and provides a strong platform for the future study of schistosome or microbial factors in the modulation of inflammatory disease.
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Schistosoma
Intestine
T Helper 2
Regulatory B cell
Immunemodulation
Chronic infection
All authors
Costain, A.H.
Supervisor
Smits, H.H.; MacDonald, A.
Committee
Roestenberg, M.; Samson, J.; Kuijper, E.J.; Thornton, D.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2023-02-02
ISBN (print)
9789464196214

Funding

Sponsorship
The final year of this thesis was supported by the IIT Graduate program, LUMC.