title: Epithelial cells activate plasmacytoid dendritic cells improving their anti-HIV activity.
abstract: Plasmacytoid dendritic cells (pDCs) play a major role in anti-viral immunity by virtue of their ability to produce high amounts of type I interferons (IFNs) and a variety of inflammatory cytokines and chemokines in response to viral infections. Since recent studies have established that pDCs accumulate at the site of virus entry in the mucosa, here we analyzed whether epithelial cells were able to modulate the function of pDCs. We found that the epithelial cell lines HT-29 and Caco-2, as well as a primary culture of human renal tubular epithelial cells (HRTEC), induced the phenotypic maturation of pDCs stimulating the production of inflammatory cytokines. By contrast, epithelial cells did not induce any change in the phenotype of conventional or myeloid DCs (cDCs) while significantly stimulated the production of the anti-inflammatory cytokine IL-10. Activation of pDCs by epithelial cells was prevented by Bafilomycin A1, an inhibitor of endosomal acidification as well as by the addition of RNase to the culture medium, suggesting the participation of endosomal TLRs. Interestingly, the cross-talk between both cell populations was shown to be associated to an increased expression of TLR7 and TLR9 by pDCs and the production of LL37 by epithelial cells, an antimicrobial peptide able to bind and transport extracellular nucleic acids into the endosomal compartments. Interestingly, epithelium-activated pDCs impaired the establishment of a productive HIV infection in two susceptible target cells through the stimulation of the production of type I IFNs, highlighting the anti-viral efficiency of this novel activation pathway.
authors.affiliation: Centro Nacional de Referencia para el SIDA, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Christian
authors.initials: C
authors.lastname: Rodriguez Rodrigues
authors.forename: Mercedes
authors.initials: M
authors.lastname: Cabrini
authors.forename: Federico
authors.initials: F
authors.lastname: Remes Lenicov
authors.forename: Juan
authors.initials: J
authors.lastname: Sabatté
authors.forename: Ana
authors.initials: A
authors.lastname: Ceballos
authors.forename: Carolina
authors.initials: C
authors.lastname: Jancic
authors.forename: Silvina
authors.initials: S
authors.lastname: Raiden
authors.forename: Matías
authors.initials: M
authors.lastname: Ostrowski
authors.forename: Claudia
authors.initials: C
authors.lastname: Silberstein
authors.forename: Jorge
authors.initials: J
authors.lastname: Geffner
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D006678:HIV / Q000378:metabolism*; D015658:HIV Infections / Q000628:therapy*; D006801:Humans; D007249:Inflammation; D007372:Interferons / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D010641:Phenotype
chemical_list: D018925:Chemokines; D003470:Culture Media; D016207:Cytokines; D018942:Macrolides; C040929:bafilomycin A1; D007372:Interferons