Mouser, Emily, Pollakis, Georgios 
ORCID: 0000-0002-9659-5461, Smits, Hermelijn, Thomas, Jordan ORCID: 0000-0003-2725-5233, Yazdanbakhsh, Maria, De Jong, Esther and Paxton, William ORCID: 0000-0001-5200-0801
(2019)
Schistosoma mansoni soluble egg antigen (SEA) and recombinant Omega-1 modulate induced CD4+ T-lymphocyte responses and HIV-1 infection in vitro.
PLoS Pathogens, 15 (9).
e1007924-.
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Mouser EIM Elements.pdf - Author Accepted Manuscript Download (1MB) | Preview |
Abstract
Parasitic helminths evade, skew and dampen human immune responses through numerous mechanisms. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we analyzed the effects that soluble egg antigen (SEA) from Schistosoma mansoni had on modulating HIV-1 infection and cytokine/chemokine production in vitro. We determined that SEA, specifically through kappa-5, can potently bind to DC-SIGN and thereby blocks DC-SIGN mediated HIV-1 trans-infection (p<0.05) whilst not interfering with cis-infection. DCs exposed to SEA whilst maturing under Th2 promoting conditions, will upon co-culture with naïve T-cells induce a T-cell population that was less susceptible to HIV-1 R5 infection (p<0.05) compared to DCs unexposed to SEA, whereas HIV-1 X4 virus infection was unaffected. This was not observed for DCs exposed to SEA while maturing under Th1 or Th1/Th2 (Tmix) promoting conditions. All T-cell populations induced by SEA exposed DCs demonstrate a reduced capacity to produce IFN-γ and MIP-1β. The infection profile of T-cells infected with HIV-1 R5 was not associated with down-modulation of CCR5 cell surface expression. We further show that DCs maturing under Tmix conditions exposed to plant recombinant omega-1 protein (rω-1), which demonstrates similar functions to natural ω-1, induced T-cell populations that were less sensitive for HIV-1 R5 infection (p<0.05), but not for X4 virus infection. This inhibition associated again with a reduction in IFN-γ and MIP-1β expression, but additionally correlated with reduced CCR5 expression. We have shown that SEA parasite antigens and more specifically rω-1 can modulate HIV-1 infectivity with the potential to influence disease course in co-infected individuals.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Dendritic Cells, CD4-Positive T-Lymphocytes, T-Lymphocytes, Helper-Inducer, Animals, Humans, Schistosoma mansoni, HIV-1, HIV Infections, Egg Proteins, Receptors, CCR5, Antibodies, Helminth, Antigens, Helminth, Cytokines, Lymphocyte Activation, Virus Replication |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 06 Sep 2019 15:28 |
| Last Modified: | 19 Jan 2023 00:27 |
| DOI: | 10.1371/journal.ppat.1007924 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3053682 |
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