title: 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.
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.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Emily E I M
authors.initials: EE
authors.lastname: Mouser
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Clinical Infection, Microbiology and Immunology (CIMI), Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Georgios
authors.initials: G
authors.lastname: Pollakis
authors.affiliation: Department of Parasitology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Harnett
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Esther C
authors.initials: EC
authors.lastname: de Jong
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Clinical Infection, Microbiology and Immunology (CIMI), Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: William A
authors.initials: WA
authors.lastname: Paxton
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D015801:Helminth Proteins / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D015801:Helminth Proteins