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The Role of Haemocytes in the Immune Response of Biomphalaria glabrata against Schistosoma mansoni: Investigations into Haematopoiesis and Pattern Recognition Receptors

  • Author / Creator
    Pila, Emmanuel A
  • Snails (Gastropoda) serve as hosts for the larval development of many medically and agriculturally important digenean trematodes (parasitic flatworms), including schistosomes, blood flukes that collectively infect more than 260 million people globally. Compatibility between snails and digeneans is often very specific such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (haemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Haemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. However, very little is known about the production and maintenance of suitable haemocyte populations, as well as how these haemocytes engage their targets. Haemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors, and until recently, nothing was known about the endogenous control of haemocyte development in any gastropod model. My doctoral research focused on characterizing endogenous drivers of haematopoiesis in Biomphalaria glabrata with emphasis on the evolutionarily conserved granulins. Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. B. glabrata pro-granulin (BgGRN) was cloned, expressed and functionally characterized. Using quantitative real-time polymerase chain reactions and Western blots, I found that endogenous BgGRN expression is induced at the early stages of S. mansoni infection. Recombinant BgGRN induced proliferation of B. glabrata haemocytes, specifically driving the production of an adherent haemocyte subset that participates centrally in the anti-digenean defence response. Additionally, I demonstrated that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing haemocyte proliferation with BgGRN. This reversal of the susceptible phenotype resulted in a 54% reduction in the number of snails successfully infected by week 7 post-challenge. Further analysis revealed that the adherent haemocytes induced by BgGRN were unique, particularly in their expression of a B. glabrata Toll-like receptor (BgTLR). TLRs are trans-membrane proteins representing one of the groups of haemocyte surface molecules through which parasite presence is detected and the signal transduced to the haemocytes to elicit effector functions required for parasite elimination. BgTLR was also found to be highly expressed at the early stages of S. mansoni infection like BgGRN, and experimental knockdown of this TLR resulted in loss of resistance in 43% of the resistant snails challenged. Taken together, these studies (of factors that drive haemocyte proliferation and differentiation, and haemocyte surface molecules that facilitate engagement of haemocytes) significantly advance the understanding of snail immunity with respect to schistosomes, and may one day facilitate the development of tools for snail control and consequently improve the control of schistosomiasis

  • Subjects / Keywords
  • Graduation date
    2018-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3Q52FT9B
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
  • Specialization
    • Public Health
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Stafford, James (Biological Sciences)
    • Neumann, Norman (School of Public Health)
    • Keddie, Andrew (Biological Sciences)
    • Yoshino, Timothy (University of Wisconsin - Madison)