title: Plasma and mucosal fluid from HIV type 1-infected patients but not from HIV type 1-exposed uninfected subjects prevent HIV type 1-exposed DC from infecting other target cells.
abstract: Highly exposed persistently seronegative (HEPS) individuals have previously been shown to mount HIV-1-specific humoral and cellular immune responses in the mucosa, despite their uninfected status. It is thus possible that HEPS individuals are protected from HIV-1 infection at the mucosal level. Recent work supports the hypothesis that dendritic cells are involved in the establishment of a mucosal HIV-1 infection as well as the dissemination to other target cells. However, no previous study has investigated if samples collected from HEPS individuals have the capacity to prevent HIV-1 infection in the presence of dendritic cells in vitro. We therefore established an assay that measures HIV-1 neutralization in cocultures of HIV-1-exposed dendritic cells (DC) and PBMC. Plasma and cervicovaginal lavage (CVL) samples from HIV-1-infected patients and HEPS individuals, enrolled in a well-characterized sex worker cohort in Kenya, were evaluated. Most plasma and CVL samples of HIV-1-infected patients neutralized HIV-1 in the DC/PBMC cocultures. Neither plasma nor CVL samples of most HEPS individuals had this capacity. However, they readily neutralized HIV-1 infection of PBMC alone. This may suggest that protection against HIV-1 infection in HEPS individuals occurs prior to interaction between HIV-1-exposed DC and other target cells.
authors.affiliation: Infectious Diseases Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden. johan.soderlund@ki.se
authors.forename: Johan
authors.initials: J
authors.lastname: Söderlund
authors.forename: Taha
authors.initials: T
authors.lastname: Hirbod
authors.forename: Anna
authors.initials: A
authors.lastname: Smed-Sörensen
authors.forename: Ulrika
authors.initials: U
authors.lastname: Johansson
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Francis
authors.initials: F
authors.lastname: Plummer
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Spetz
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
mesh_terms: D002478:Cells, Cultured; D002584:Cervix Uteri / Q000276:immunology; D018920:Coculture Techniques; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000517:prevention & control / Q000635:transmission / Q000821:virology*; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D018928:Immunity, Mucosal; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D009500:Neutralization Tests; D011477:Sex Work; D014621:Vagina / Q000276:immunology
chemical_list: D004279:DNA, Viral