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Expression Profile of Human Fc Receptors in Mucosal Tissue: Implications for Antibody-Dependent Cellular Effector Functions Targeting HIV-1 Transmission.

Cheeseman HM, Carias AM, Evans AB, Olejniczak NJ, Ziprin P, King DF, Hope TJ, Shattock RJ - PLoS ONE (2016)

Bottom Line: 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.We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria.

View Article: PubMed Central - PubMed

Affiliation: Imperial College London, Department of Medicine, Section of Virology, Group of Mucosal Infection and Immunity, London, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus

Localization of CD56+ cells within three different mucosal tissue types.Deconvolution microscopy images showing location of CD56+ cells within Penile Glans (A), Ectocervical (B) and Colorectal tissue (C) and relative co-expression of FcR CD16 (i), CD32 (ii), CD64 (iii) and CD89 (iv). CD56 is shown in green, the FcR are shown in red and DAPI is shown in blue. Images taken at 40x; Scale bar set to 40 microns.
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pone.0154656.g008: Localization of CD56+ cells within three different mucosal tissue types.Deconvolution microscopy images showing location of CD56+ cells within Penile Glans (A), Ectocervical (B) and Colorectal tissue (C) and relative co-expression of FcR CD16 (i), CD32 (ii), CD64 (iii) and CD89 (iv). CD56 is shown in green, the FcR are shown in red and DAPI is shown in blue. Images taken at 40x; Scale bar set to 40 microns.

Mentions: CD56+ cells of the penile tissue were the most diffusely located effector cell type that we stained for within this tissue. Whilst the majority resided within the subepithelial lamina propria, we also observed CD56+ cells within the stratum basale and, on one occasion, a CD56+ cell was noted near the luminal border (Fig 8A). Within cervical tissue, CD56+ cells were primarily observed within the subepithelium or stratum basale (Fig 8B), whereas CD56+ cells of the colorectal tissue were, once again, found to be exclusively located within the lamina propria (Fig 8C). Across all mucosal tissues, co-localization of the effector cells and FcR were in line with the flow cytometry data (Figs 6–8 & S2–S4 Figs).


Expression Profile of Human Fc Receptors in Mucosal Tissue: Implications for Antibody-Dependent Cellular Effector Functions Targeting HIV-1 Transmission.

Cheeseman HM, Carias AM, Evans AB, Olejniczak NJ, Ziprin P, King DF, Hope TJ, Shattock RJ - PLoS ONE (2016)

Localization of CD56+ cells within three different mucosal tissue types.Deconvolution microscopy images showing location of CD56+ cells within Penile Glans (A), Ectocervical (B) and Colorectal tissue (C) and relative co-expression of FcR CD16 (i), CD32 (ii), CD64 (iii) and CD89 (iv). CD56 is shown in green, the FcR are shown in red and DAPI is shown in blue. Images taken at 40x; Scale bar set to 40 microns.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4862624&req=5

pone.0154656.g008: Localization of CD56+ cells within three different mucosal tissue types.Deconvolution microscopy images showing location of CD56+ cells within Penile Glans (A), Ectocervical (B) and Colorectal tissue (C) and relative co-expression of FcR CD16 (i), CD32 (ii), CD64 (iii) and CD89 (iv). CD56 is shown in green, the FcR are shown in red and DAPI is shown in blue. Images taken at 40x; Scale bar set to 40 microns.
Mentions: CD56+ cells of the penile tissue were the most diffusely located effector cell type that we stained for within this tissue. Whilst the majority resided within the subepithelial lamina propria, we also observed CD56+ cells within the stratum basale and, on one occasion, a CD56+ cell was noted near the luminal border (Fig 8A). Within cervical tissue, CD56+ cells were primarily observed within the subepithelium or stratum basale (Fig 8B), whereas CD56+ cells of the colorectal tissue were, once again, found to be exclusively located within the lamina propria (Fig 8C). Across all mucosal tissues, co-localization of the effector cells and FcR were in line with the flow cytometry data (Figs 6–8 & S2–S4 Figs).

Bottom Line: 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.We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria.

View Article: PubMed Central - PubMed

Affiliation: Imperial College London, Department of Medicine, Section of Virology, Group of Mucosal Infection and Immunity, London, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus