Parasitic helminths and HIV-1 infection: the effect of immunomodulatory antigens

E.E.I.M. Mouser

Research output: PhD ThesisPhD-Thesis - Research and graduation internal

Abstract

In many regions of the world co-infection with parasitic helminths and HIV-1 is common. Both pathogens have major implications for the host immune system, helminths possess immunomodulatory properties whilst HIV-1 infects and kills immune cells. Currently very little is known regarding what effects the immunomodulatory properties of helminths have on HIV-1. In this thesis we studied the effect of three specific helminth products on HIV-1 infection and replication utilizing in vitro model systems.
We demonstrate that Schistosoma mansoni soluble egg antigen (SEA) can potently bind C-type lectin receptor DC-SIGN and inhibit HIV-1 trans-infection of CD4⁺ lymphocytes. Additionally, both antigens derived from adult Brugia malayi worms (BmA) and lactoferrin found in colorectal mucus were shown to block DC-SIGN mediated HIV-1 trans-infection, whilst the purified Excretory Secretory molecule 62 (ES-62) from adult Acanthocheilonema viteae does not.
Helminths are known to modulate immune responses. DCs encountering antigens/pathogens mature and induce a T-cell response. We demonstrate that the presence of SEA during DC maturation results in the induction of T-cell populations less susceptible to CCR5-using but not CXCR4-using HIV-1. The component of SEA responsible for this is omega-1. Contrary to SEA, the presence of BmA or ES-62 during DC maturation did not result in the induction of T-cells with an altered susceptibility for HIV-1 infection.
These results indicate that parasitic helminth products have the potential to limit HIV-1 infection and replication. Hence, studying the immunomodulatory properties of helminths may result in the development of new strategies aimed at curtailing HIV-1 transmission or disease progression.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
  • Berkhout, B., Supervisor, External person
  • Paxton, W.A., Supervisor
  • de Jong, Esther C., Co-supervisor
  • Pollakis, G., Co-supervisor
Award date19 May 2016
Print ISBNs9789461825797
Publication statusPublished - 2016

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