Characterization of CCL20 secretion by human epithelial vaginal cells: involvement in Langerhans cell precursor attraction

Abstract

Mucosa represents the main site of pathogen/cell interactions. The two main types of cells forming the epithelial structure [epithelial cells and Langerhans cells (LC)] coordinate the first defense responses to avoid infection. To evaluate the involvement of epithelial cells in the early steps leading to a specific adaptive immune response, we have studied the interactions between vaginal epithelial and LC through the establishment of a human vaginal epithelial mucosa. We demonstrate that normal human vaginal epithelial cells constitutively secrete the chemokine macrophage inflammatory protein 3alpha/CC chemokine ligand 20 (CCL20), known to recruit LC precursors (LCps) selectively via its cognate CC chemokine receptor 6 (CCR6). This secretion is up-regulated by the proinflammatory cytokine interleukin-1beta through the nuclear factor-kappaB pathway. Similar results were obtained with the human vaginal epithelial cell line SiHa, which displays numerous homologies with normal vaginal cells. The chemotactic activity of the secreted CCL20 was demonstrated by its ability to attract LCp CCR6+. Moreover, the use of neutralizing polyclonal antibodies directed against the CCL20 molecule abolished this migration completely, suggesting that CCL20 is the main attracting factor for LCps, which is produced by the vaginal cells. These data indicate that vaginal epithelial cells play an important role in the immunological defense by attracting immune cells to the site of epithelial/pathogen contact.

CpG Oligodeoxynucleotides Facilitate Delivery of Whole Inactivated H9N2 Influenza Virus via Transepithelial Dendrites of Dendritic Cells in Nasal Mucosa

“…The typical lines of supporting evidence were from the stratified epithelia of tonsils, skin, and vagina during inflammation. Complementary chemokine gradients were found within the epithelium itself, and CCL20 expression in the most apical cell layers accounts for DC migration of Langerhans cell precursors into the epithelium (65,66). For the single-layered epithelium of the intestine, the results from our (data not shown) and other studies (67) also support the above-described views.…”

Barriers to mucosal transmission of immunodeficiency viruses

“…36,49,50 Collectively, these early recruited cells are important mediators of innate defenses and inflammation, in addition to initiating and linking innate and adaptive immunity. In addition, the mucosally recruited plasmacytoid DCs were shown to produce copious amounts of macrophageinflammatory protein-1␣/␤ (CCL3/4) and type I interferon (IFN)-␣/␤, 36 which have been shown to have a wide variety of antiviral effects capable of impacting HIV replication through numerous mechanisms, including induction of apolipoprotein B mRNAediting enzyme catalytic polypeptide-like 3G, latent endoribonuclease through the expression of oligoadenylate synthetase, myxovirus-family proteins, and other IFN-inducible proteins.…”

Mucosal safety of PHI-443 and stampidine as a combination microbicide to prevent genital transmission of HIV-1

“…Detectable levels of these b-chemokines are present in cervical fluid (45). The recruitment of LCs in the vaginal mucosa is mediated by the most potent chemokine MIP-1a (26). Local immune reactions influence the concentrations of HIV-1 in the cervical compartment.…”

“…They have anatomic, phenotypic, and functional properties that allow for interactions to occur with HIV-1 and genital mucosal epithelium. Cytokines/chemokines that activate macrophages, such as interleukin (IL)-1b, IL-8, and macrophage inflammatory protein (MIP)-1b, those acting on other effectors, such as epithelial neutrophil-activating peptide (ENA)-78, granulocyte colony-stimulating factor (G-CSF), granulocytemacrophage colony-stimulating factor (GM-CSF), and IL-8 on granulocytes, and monocyte/macrophage chemoattractant protein (MCP)-1, MIP-1a, MIP-3a, and regulated upon activation of normal T-cell expressed and secreted (RANTES) on LCs, are thought to mediate mucosal inflammation and also play a role in the dissemination of HIV-1 infection by genital transmission (22)(23)(24)(25)(26)(27)(28). Consequently, the ability of PHI-443 and stampidine to affect the levels of key cytokines and chemokines in culture media was quantitated by means of a multiplexed chemiluminescence-based immunoassay.…”