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Title: Impact of helminth infection on antimycobacterial immune responses in UK migrants
Author: Anwar, S.
ISNI:       0000 0004 6425 4720
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 2017
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Tuberculosis and helminth infections are co endemic in many parts of the world. This geographical overlap has led to the hypothesis that helminth infections could exacerbate the effects of Mycobacterium tuberculosis (Mtb) infection. Anthelmintic treatment has been observed to be associated with improved mycobacterial cellular responses and decreases in the frequency of Treg cells. The consequence of this immunomodulation may affect the ability of the host to restrict the growth of mycobacteria or mycobacterial killing. This study aims at investigating the modulations of the immune response profile of latent tuberculosis (LTBI) and helminth co-infected patients and whether these modulations are associated with a decrease in mycobacterial growth inhibition using a mycobacterial growth inhibition assay (MGIA).UK migrants attending University College Hospital London, UK with eosinophilia or suspected/diagnosed helminth infection (Strongyloides spp and Schistosoma spp) and/or LTBI were bled at recruitment (before anthelmintic treatment) and 4 months after completing anthelmintic treatment. Helminth infected patients displayed poor growth inhibition on MGIA which was improved after anthelmintic treatment which indicated this immunomodulation might be helminth mediated. The percentage of CD4+ T cells expressing IFNg, TNFa and IL-2 were quantified by flow cytometry in PPD and ESAT-6/CFP-10 stimulated PBMC and anthelmintic treatment was observed to increase the frequency of CD4+IFNg response. LTBI-helminth coinfection was associated with significantly elevated levels of proinflammatory and lower levels of anti-inflammatory cytokines after they were treated. IP- 10 was significantly upregulated and MCP-1 was significantly downregulated in LTBIhelminth coinfected patients after anthelmintic treatment. The effect of IL-10 and TGFb on MGIA were observed and suggested an immunoregulatory role in helminth infected patients. Gene expression analysis by qRT-PCR showed varied responses and showed significant fold changes of CXCL-10, arginase 1 and CD163 after the treatment. MGIA and multiple immune parameters have shown that helminth infection can modulate a variety of Mtb specific immune responses.
Supervisor: Dockrell, H. M. Sponsor: Commonwealth Scholarship Commission
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral