Impact of the microbiome on mast cell-mediated protective immune responses in Trichinella spiralis infection

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2021
Thesis identifier
  • T16174
Person Identifier (Local)
  • 201990944
Qualification Level
Qualification Name
Department, School or Faculty
  • Helminths are parasitic worms that pose a significant threat globally. Soil-transmitted helminths are responsible for more disease and infection cases than tuberculosis or malaria in developing countries, infecting over 1.45 billion people, resulting in 5.18 million disability adjusted life years (DALY) lost and 4.98 million years lived with disease (YLD) per year. Infection of livestock is a significant problem as meat and dairy cattle and sheep can provide an additional vector for infection as well as causing significant losses in livestock productivity costing over €1.8 billion in the EU. Thus, understanding the mechanisms that are required to protect against these infections is important, while the role of Th2 responses have been well characterised, it is still unclear how the responses are initiated. Mast cells have been shown to play a key role in the expulsion of parasites, and initiating and amplifying immune responses through antigen presentation and cytokine production. First, we aimed to evaluate the role of helminths in antibody-independent MC activation. We hypothesise that antibody independent mast cell activation can occur in response to helminth infections. Following harvesting bone marrow and peritoneal derived mast cells from WT and MC deficient mice, we found evidence of IgE-independent mast cell activation in both bone marrow and peritoneal derived mast cells. Cytokines, such as IL-4, IL-9, and IL-10, that are needed for parasite expulsion were found to be unchanged in Trichinella spiralis stimulated IgE-independent mast cell activation compared to IgE-dependent activation. The microbiome of the gut has the highest abundance and diversity of microorganisms and it provides crucial functions that humans don’t possess in nutritional and physiological influences. Helminths can influence the microbial composition of the microbiome via the antimicrobial properties of helminth excretory/secretory products. The gut microbiome has been shown to be able to influence immune responses to helminths as well, however the extent of this effect is unclear. We aimed to evaluate the effects of the gut microbiome in mast cell mediated protective and pathological immune responses and enteropathy following Trichinella spiralis infection. WT and mast cell-deficient mice were treated with antibiotics and were compared to their untreated counterparts. We propose that the absence of the gut microbiome causes significant reduction in MC mediated immune response in WT mice and that MC deficient mice also show alterations in the helminth induced immune response as well as parasite expulsion. Analysis of the cell count in MLN of both C57 and mast cell deficient Wsh mice revealed that the lack of the intestinal microbiome prevents cell migration to the MLN hindering the adaptive immune response to T. spiralis infection. However, no change in MLN cell numbers from uninfected to infected suggest low naïve T cell population in absence of microbiome. In conclusion it can be seen that mast cells can be activated in an antibody independent manner and this induces the release of cytokines which could play a role in amplification and polarisation of T cell responses. Furthermore, the microbiome may play a role in potentiating protective and pathological immune responses in the gut and thus may influence the activation of mast cells or their interactions with other elements of the immune response. TLR, OX40, and selective reconstitution of microbial communities of the gut could be a focus for future studies to provide further insight into the mechanisms and relationships between the microbiome and MC in response to helminths.
Advisor / supervisor
  • Lawrence, Catherine
Resource Type
Embargo Note
  • This thesis is restricted to Strathclyde users only.