Brugia malayi Antigen (BmA) inhibits HIV-1 trans-infection but neither BmA nor ES-62 alter HIV-1 infectivity of DC induced CD4+ Th-cells

Mouser, Emily E. I. M. and Pollakis, Georgios and Yazdanbakhsh, Maria and Harnett, William and de Jong, Esther C. and Paxton, William A. (2016) Brugia malayi Antigen (BmA) inhibits HIV-1 trans-infection but neither BmA nor ES-62 alter HIV-1 infectivity of DC induced CD4+ Th-cells. PLOS One, 11 (1). ISSN 1932-6203

[img]
Preview
Text (Mouser-etal-PLOSOne-2016-Brugia-malayi-Antigen-BmA-inhibits-HIV-1-trans-infection-but-neither-BmA)
Mouser_etal_PLOSOne_2016_Brugia_malayi_Antigen_BmA_inhibits_HIV_1_trans_infection_but_neither_BmA.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo

Download (1MB)| Preview

    Abstract

    One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA) and excretory-secretory product 62 (ES-62) from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th) cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs.