Any of the four
dengue serotypes can cause a severe disease, partly due to systemic
inflammation orchestrated by mediators like
cytokines and
chemokines. We addressed the role of CCR1 and its
ligands CCL3/MIP-1α and CCL5/
RANTES in
dengue infection using three different approaches: an ex vivo model exploring memory immune response in subjects with a well characterized
dengue immune background, an in vivo study in patients with primary or secondary
dengue infection, and an approach in fatal
dengue. CCR1 and CCL3/MIP-1α gene expression showed differences after homotypic and heterotypic challenge according to
dengue immune background of subjects, in correspondence with previous observations in Cuban
dengue outbreaks. CCL5/
RANTES gene expression was higher after homotypic challenge. CCR1 and CCL3/MIP-1α gene expression was higher in patients with
secondary infection during critical days of the
dengue disease, while the increase in
RANTES expression started earlier than the observed for CCR1 and CCL3/MIP-1α. CCR1 and CCL3/MIP-1α gene expression was as high in brain as in spleen tissue from necropsy. Our results confirm the strong influence of previous immunity in subsequent
dengue infections, and confer a possible pathogenic role to CCR1 and CCL3/MIP-1α in
dengue disease and a possible protective role for CCL5/
RANTES, probably through CCR5 interaction.