Hematopoietic niches promote initiation of malaria transmission and evasion of chemotherapy

Lee, Rebecca Sarah (2017) Hematopoietic niches promote initiation of malaria transmission and evasion of chemotherapy. PhD thesis, University of Glasgow.

Due to Embargo and/or Third Party Copyright restrictions, this thesis is not available in this service.

Abstract

The transmission of the malaria parasite (Plasmodium spp) is effected by a small proportion of the population that commit to sexual development forming either male or female gametocytes. Currently front-line anti-malarials are developed to treat the asexual life stage parasitising mature erythrocytes. While circulating mature erythrocytes form a relatively homogenous population, it has been recently established that Plasmodium spp can colonise progenitor cells in the erythroid lineage. I hypothesised that these tissue-resident erythroid precursors may form a niche for preferential development of gametocytes, and therefore developed a quantitative approach to enumerate Plasmodium-infected erythropoietic intermediate cells in haematopoietic tissues. We demonstrate that within erythropoietic tissues, early reticulocytes preferentially drive commitment to gametocytogenesis, with the splenic niche contributing the quantifiable majority of gametocytes. Furthermore, this same erythropoetic niche offers the parasite protection against antimalarial drug treatment and, as such, may serve as origins of recrudescent infection and continuing transmission. My data therefore demonstrate that host cell phenotype and location play an active role in determining the developmental fate of malaria parasites and furthermore suggests a mechanism for the persistence of malaria parasites.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Plasmodium.
Subjects: Q Science > Q Science (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Parasitology
Funder's Name: UNSPECIFIED
Supervisor's Name: Brewer, Professor James and Waters, Professor Andy
Date of Award: 2017
Embargo Date: 7 September 2018
Depositing User: Ms Rebecca Lee
Unique ID: glathesis:2017-8370
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 07 Sep 2017 13:30
Last Modified: 21 Sep 2017 12:36
URI: http://theses.gla.ac.uk/id/eprint/8370

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