UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Novel Mechanisms of Antihelminth Immunity

Entwistle, Lewis James; (2018) Novel Mechanisms of Antihelminth Immunity. Doctoral thesis (Ph.D), UCL (University College London). Green open access

[img]
Preview
Text
Entwistle_thesis.pdf - Submitted version

Download (8MB) | Preview

Abstract

Intestinal helminths are highly prevalent worldwide, infecting approximately a third of the world’s population, causing significant host morbidity. With no current vaccines, a limited number of effective chemotherapeutic drugs available and the emergence of drug-resistant helminths, it is essential to further our understanding of the mechanisms of antihelminth immunity. Our current understanding of antihelminth immunity places the type 2 immune response at the forefront of protection, with type 2 cytokines orchestrating and activating a plethora of immune and non-immune cells to mediate parasite expulsion. The naturally occurring intestinal helminth Heligmosomoides polygyrus establishes a chronic infection in many inbred naïve mice, with resistance to a challenge infection established following drug-cure. This experimental model allows us to identify novel mechanisms of drug-induced resistance, relative to susceptibility. In this thesis, we utilised next generation sequencing technology to identify two novel mechanisms of antihelminth immunity. Firstly, we determined that the enzyme phospholipase A2 group 1B (PLA2g1B) is an endogenous anthelmintic, upregulated in intestinal epithelial cells of resistant mice. We demonstrated that PLA2g1B was essential for resistance to H. polygyrus and that PLA2g1B directly cleaves phospholipids off infective H. polygyrus larvae. Secondly, we identified that the microRNAs miR-99a-5p, miR-148a-3p and miR-155-5p were upregulated in mice resistant to H. polygyrus during infection and were also essential for functional immunity. In summary, we have identified and characterised two novel mechanisms of antihelminth immunity and propose a model of tissue memory, essential for acquired resistance to H. polygyrus.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Novel Mechanisms of Antihelminth Immunity
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10041378
Downloads since deposit
71Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item