Epithelial Cells Activate Plasmacytoid Dendritic Cells Improving Their Anti-HIV Activity

C. RODRIGUEZ RODRIGUES; M. CABRINI; F. REMES LENICOV; J. SABATTÉ; A. CEBALLOS; C. JANCIC; S. RAIDEN; M. OSTROWSKI; C. SILBERSTEIN; J. GEFFNER

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2011 vol. 6 p. 28709 - 28722

1932-6203

Plasmacytoid dendritic cells (pDCs) play a major role in anti-viral immunity by virtue of their ability to produce high amountsof type I interferons (IFNs) and a variety of inflammatory cytokines and chemokines in response to viral infections. Sincerecent studies have established that pDCs accumulate at the site of virus entry in the mucosa, here we analyzed whetherepithelial cells were able to modulate the function of pDCs. We found that the epithelial cell lines HT-29 and Caco-2, as wellas a primary culture of human renal tubular epithelial cells (HRTEC), induced the phenotypic maturation of pDCs stimulatingthe production of inflammatory cytokines. By contrast, epithelial cells did not induce any change in the phenotype ofconventional 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 bythe addition of RNase to the culture medium, suggesting the participation of endosomal TLRs. Interestingly, the cross-talkbetween both cell populations was shown to be associated to an increased expression of TLR7 and TLR9 by pDCs and theproduction of LL37 by epithelial cells, an antimicrobial peptide able to bind and transport extracellular nucleic acids into theendosomal compartments. Interestingly, epithelium-activated pDCs impaired the establishment of a productive HIVinfection in two susceptible target cells through the stimulation of the production of type I IFNs, highlighting the anti-viralefficiency of this novel activation pathway.