Evaluation of the role of mast cells in parasitic infection

  • Faiz Abdulaziz S Alfaiz

Student thesis: Doctoral Thesis

Abstract

Mast cells (MCs) are important for controlling both bacterial and parasitic infections, including those caused by helminths. However, their role in combatting these infections is unclear. MCs have been shown to be essential for the successful expulsion of Trichinella spiralis worms and play a role in mounting the immune response towards a T helper 2 type. Intestinal infection with parasitic worms is associated with mastocytosis and the activation and release of specific mediators and cytokines. In this case, MCs play an essential role in the successful expulsion of gastrointestinal worms via their release of mediators that serve the central function of protecting a host from these parasites. Specifically, the functions of MCs in the expulsion of T. spiralis were investigated using MC deficient c-kit mutant KitW/W-v(W/W-v) models. However, in addition to MC deficiency, these mice have a number of other abnormalities, including anaemia and a lack of interstitial cells of Cajal. Hence, there is a need to identify a model of MC deficiency that is not associated with other abnormalities that could affect the interpretation of results. The aim of the present study was to investigate the role of MCs in the immune response of mice to a parasitic infection of T. spiralis. Immune responses were explored in two recently developed strains of MC-deficient mice, the c-kit model C57BL/6-KitW-sh/W-sh (Wsh/Wsh) mice and an inducible mast cell-deficient model, Mas-TRECK, to determine the role of mast cells in protection against the parasite. These mice were infected with T. spiralis larvae, and the progression of the infection and the immune responses generated were examined via the enumeration of worms and the analysis of the associated intestinal pathology, cytokine production and antibody responses.The results obtained from mast cell deficient Wsh/Wsh mice with low-level infection resulted in a significant worm burden in these mice compared to wild-type mice that showed complete expulsion of the parasite. This suggests that the delay was potentially caused by dose dependent effect as a high dose did not show a significant delay in the expulsion of T. spiralis worms. In addition, the development of enteropathy and lengths of both villi and crypts were similar in both the lower and higher infection groups, in both wild-type and Wsh/Wsh mice.The immune responses were similar in wild-type and Wsh/Wsh mice as assessed by antigen-specific IgG1 levels, the total IgE levels and IL-4 levels. Moreover, Wsh/Wsh mice in both levels of infection were able to induce a significant marked mastocytosis, but they did not have significantly lower levels of mMCP-1 compared to wild-type mice. The results obtained from Mas-TRECK mice models showed no statistically significant differences between these mice and wild-type mice in the expulsion of T. spiralis worms. The enteropathy in Mas-TRECK mice following infection with T.spiralis was not significantly improved.In addition, the infection of Mas-TRECK mice did not induce a change in IgG2a levels compared with BALB/c mice, and no significant differences were observed in IgE levels or IL-4 levels in Mas-TRECK mice, compared with wild-type. In addition, Mas-TRECK were able to induce mastocytosis and did not have significantly lower levels of mMCP-1 following infection with T. spiralis, although they are considered to be MC-deficient, which suggests that MMCs may not be completely depleted in these mice. Mast cell activation was assessed using IgE-dependent MC activation to evaluate the ability of helminth antigens to activate mast cells through an immunoglobulin independent mechanism. An in vitro culture of bone marrow-derived mast cells(BMMCs) and peritoneal mast cells (PCMCs) used. Although cultured human MCs require stem cell factor (SCF) for growth, the expansion and growth of mouse MCs from bone marrow progenitor
Date of Award1 Jan 2017
LanguageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorCatherine Lawrence (Supervisor) & Katharine Carter (Supervisor)

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