Expression of DC-SIGN by Dendritic Cells of Intestinal and Genital Mucosae in Humans and Rhesus Macaques

Most DC-SIGNR transcripts at mucosal HIV transmission sites are alternatively spliced isoforms

“…We therefore tested for vaginal and rectal expression of DC-SIGNR using a more sensitive molecular technique, nested RT-PCR, and found DC-SIGNR mRNA in all 13 vaginal and four rectal biopsies tested (Tables 1 and 2). As predicted from the immunohistochemical analyses, 5,6 nested RT-PCR also demonstrated the consistent presence of DC-SIGN mRNA when we analyzed 12 of the vaginal and two of the rectal biopsies (Table 2). For control purposes, we also analyzed DC-SIGN and DC-SIGNR mRNA expression by in vitro monocyte-derived DCs of four additional individuals.…”

“…5,6 Nevertheless, our finding that certain DC-SIGNR genotypes correlate with the risk for HIV-1 infection 21 may signify the presence of this molecule at the site of viral invasion. We therefore tested for vaginal and rectal expression of DC-SIGNR using a more sensitive molecular technique, nested RT-PCR, and found DC-SIGNR mRNA in all 13 vaginal and four rectal biopsies tested (Tables 1 and 2).…”

“…17 Based on the association of certain DC-SIGNR genotypes with susceptibility to HIV-1 infection in vivo, 21 we hypothesized that alternative forms of DC-SIGNR are present in the genital and rectal mucosa, which exert influence on the acquisition of HIV-1 infection during sexual contact. Despite the lack of prior immunohistochemical evidence for DC-SIGNR in the mucosa, 5 we speculated that if, for example, soluble isoforms dominated locally, immunohistochemistry may not have been a sufficiently sensitive detection technique. Therefore, we applied a more sensitive limiting dilution nested PCR to identify DC-SIGNR mRNA in vaginal and rectal biopsies, and estimated the contribution of DC-SIGNR isoforms to the entire pool of mucosal DC-SIGN and DC-SIGNR.…”

On the potential involvement of CD11d in co-stimulating the production of interferon- by natural killer cells upon interaction with neutrophils via intercellular adhesion molecule-3

“…Highly purified neutrophils, NK cells and slanDC were isolated and cultured for 18 h as previously described, 5 with or without 100 ng/mL LPS plus the IL-15/IL-18 combination (both at 10 ng/mL), in the presence of 10 mg/mL αCD11a/CD18 efalizumab, a humanized IgG1 antibody derived from the murine MHM24 clone 10 which, in preliminary experiments, confirmed its ability to prevent the binding of CD11a to either ICAM-1 11 or ICAM-3 12 in a specific T-cell adhesion assay 13 , 10 mg/mL αCD18 or αCD18 F(ab')2 fragments [clone IB4 (mouse IgG2a)], 10 mg/mL αDC-SIGN [clone 120507 (mouse IgG2b) 14 or clone MR-1 (mouse IgG1) 15 ], as well as corresponding isotype control antibodies. Monocytederived dendritic cells (moDC) were generated as previously described.…”

Polymeric Anti‐HIV Therapeutics

“…[118][119][120][121] More specifically, the C-type lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing non-integrin) interacts with the mannose glycans on the envelope protein gp120 and binds to HIV. [120,122] As depicted in Figure 8b, polymeric antagonists that inhibit the transport of HIV to the lymphoid tissue, have been developed that mimic the N-linked mannose arrangement on gp120 and therefore block the interaction of glycans on HIV with DC-SIGN.…”