Promotie
Exploring host-immune-microbial interactions during intestinal schistosomiasis
- A.H. Costain
- Datum
- donderdag 2 februari 2023
- Tijd
- Locatie
-
Academiegebouw
Rapenburg 73
2311 GJ Leiden
Promotor(en)
- Prof.dr. H. Smits
- Prof.dr. A. MacDonald (University Of Manchester)
Samenvatting
Schistosomes are parasitic flatworms that, over the course of millennia, have evolved to thrive within their mammalian host by, among other things, adopting peculiar lifecycle stages and manipulating host immune processes. During schistosome infections, hundreds of parasite eggs transit across the intestinal wall, triggering an exuberant immune response and considerable damage to the host. Thus, to enhance host fitness and thereby promote their own survival, schistosomes employ a variety of techniques to calibrate host immunity. This includes the production of their own immunomodulatory molecules, and potentially, gaining assistance from intestinally derived signals such as the microbiota. In this thesis, we dissect 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, we provide a concise narrative of schistosome associated immune profiles over time and across multiple tissue sites (liver, intestine, spleen, and mesenteric lymph nodes), and offer insight into the contribution of CD11c+ cells and Type I interferons in immune response instruction.
Focusing on the intestine, we show elevated intestinal permeability during chronic and high dose egg producing infections and reveal the character of the colonic immune system and host microbiota during infection. Significantly, using germ-free mice and faecal transplants, we provide evidence that the schistosome infection associated microbiota can influence host Immunity. Together, our data elevates 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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Algemene informatie
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