Abstract
The majority of new Human Immunodeficiency Virus (HIV)-1 infections are acquired via sexual transmission at mucosal surfaces. Partial efficacy (31.2%) of the Thai RV144 HIV-1 vaccine trial has been correlated with Antibody-dependent Cellular Cytotoxicity (ADCC) mediated by non-neutralizing antibodies targeting the V1V2 region of the HIV-1 envelope. This has led to speculation that ADCC and other antibody-dependent cellular effector functions might provide an important defense against mucosal acquisition of HIV-1 infection. However, the ability of antibody-dependent cellular effector mechanisms to impact on early mucosal transmission events will depend on a variety of parameters including effector cell type, frequency, the class of Fc-Receptor (FcR) expressed, the number of FcR per cell and the glycoslyation pattern of the induced antibodies. In this study, we characterize and compare the frequency and phenotype of IgG (CD16 [FcγRIII], CD32 [FcγRII] and CD64 [FcγRI]) and IgA (CD89 [FcαR]) receptor expression on effector cells within male and female genital mucosal tissue, colorectal tissue and red blood cell-lysed whole blood. The frequency of FcR expression on CD14+ monocytic cells, myeloid dendritic cells and natural killer cells were similar across the three mucosal tissue compartments, but significantly lower when compared to the FcR expression profile of effector cells isolated from whole blood, with many cells negative for all FcRs. Of the three tissues tested, penile tissue had the highest percentage of FcR positive effector cells. Immunofluorescent staining was used to determine the location of CD14+, CD11c+ and CD56+ cells within the three mucosal tissues. We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria. The potential implication of the observed FcR expression patterns on the effectiveness of FcR-dependent cellular effector functions to impact on the initial events in mucosal transmission and dissemination warrants further mechanistic studies.
Highlights
The majority of new Human Immunodeficiency Virus (HIV-1) infections occur via sexual transmission at the mucosal portals of entry, the male and female genital tracts and the rectal mucosa [1]
Similar percentages of NKT cells (CD3+CD56+), Myeloid dendritic cells (mDC) and CD3+ T-cells were observed across the three mucosal tissue types and whole blood, a trend towards higher expression of CD3+ T-cells was observed for cells isolated penile tissue
To better understand the potential of antibody-dependent cellular effector functions to impact on initial events in mucosal HIV-1 transmission, we characterized the relative Fc Receptor (FcR) expression doi:10.1371/journal.pone.0154656.g005
Summary
The majority of new Human Immunodeficiency Virus (HIV-1) infections occur via sexual transmission at the mucosal portals of entry, the male and female genital tracts and the rectal mucosa [1]. Extensive correlates analysis of the RV144 trial identified that a reduced risk of HIV-1 acquisition was positively associated with the development of serum IgG antibodies ( IgG3) to the V1V2 region of the Env trimer able to mediate antibody-dependent cellular cytotoxicity (ADCC) [3,4,5] This positive association was negated in the presence of high levels of IgA antibodies able to block Fc-gamma receptor (FcγR) mediated ADCC through competitive binding to V1V2 [4]. These observations have led to the suggestion that ADCC activity might be an important component of prophylactic vaccines against HIV-1 and potentially a mechanistic correlate of protection in the RV144 trial [3, 6,7,8,9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
