Mucosal and plasma IgA from HIV-1-exposed uninfected individuals inhibit HIV-1 transcytosis across human epithelial cells.
HIV-1-specific IgA has been described in the genital tract and plasma of HIV-1 highly exposed, persistently seronegative (HEPS) individuals, and IgA from these sites has been shown to neutralize HIV-1. This study examines the ability of IgA isolated from HEPS individuals to inhibit transcytosis across a tight epithelial cell layer. A Transwell system was established to model HIV-1 infection across the human mucosal epithelium. The apical-basolateral transcytosis of primary HIV-1 isolates across this mucosal model was examined in the presence and the absence of IgA isolated from the genital tract, saliva, and plasma of HEPS individuals enrolled in both a sex worker cohort in Nairobi, Kenya, and a discordant couple cohort in Italy. In the absence of IgA, HIV-1 primary isolates were actively transported across the epithelial membrane and were released on the opposite side of the barrier. These transcytosed HIV-1 particles retained their ability to infect human mononuclear cells. However, IgA purified from the mucosa and plasma of HEPS individuals was able to inhibit HIV-1 transcytosis. Inhibition was seen in three of six cervicovaginal fluid samples, five of 10 saliva samples, and three of six plasma samples against at least one of the two primary HIV-1 isolates tested. IgA from low risk, healthy control subjects had no inhibitory effect on HIV-1 transcytosis. The ability of mucosal and plasma IgA to inhibit HIV-1 transcytosis across the mucosal epithelium may represent an important mechanism for protection against the sexual acquisition of HIV-1 infection in HEPS individuals.
Devito
C
C
Department of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Broliden
K
K
Kaul
R
R
Svensson
L
L
Johansen
K
K
Kiama
P
P
Kimani
J
J
Lopalco
L
L
Piconi
S
S
Bwayo
J J
JJ
Plummer
F
F
Clerici
M
M
Hinkula
J
J
D019380:Anti-HIV Agents / Q000276:immunology*; D018938:Caco-2 Cells; D015194:Diffusion Chambers, Culture / Q000379:methods; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood* / Q000502:physiology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology*; D008297:Male; D018448:Models, Immunological
D019380:Anti-HIV Agents; D007070:Immunoglobulin A