title: Role of CC chemokine receptor 1 and two of its ligands in human dengue infection. Three approaches under the Cuban situation.
abstract: 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.
authors.affiliation: Virology Department, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Pedro Kouri Institute of Tropical Medicine, Autopista Novia del Mediodia, Km 6½, La Lisa, Habana, Cuba. Electronic address: siebet@ipk.sld.cu.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sierra
authors.affiliation: Virology Department, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Pedro Kouri Institute of Tropical Medicine, Autopista Novia del Mediodia, Km 6½, La Lisa, Habana, Cuba.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Perez
authors.affiliation: Virology Department, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Pedro Kouri Institute of Tropical Medicine, Autopista Novia del Mediodia, Km 6½, La Lisa, Habana, Cuba.
authors.forename: Gissel
authors.initials: G
authors.lastname: Garcia
authors.affiliation: Virology Department, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Pedro Kouri Institute of Tropical Medicine, Autopista Novia del Mediodia, Km 6½, La Lisa, Habana, Cuba.
authors.forename: Eglys
authors.initials: E
authors.lastname: Aguirre
authors.affiliation: Virology Department, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Pedro Kouri Institute of Tropical Medicine, Autopista Novia del Mediodia, Km 6½, La Lisa, Habana, Cuba.
authors.forename: Mayling
authors.initials: M
authors.lastname: Alvarez
authors.affiliation: Virology Department, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Pedro Kouri Institute of Tropical Medicine, Autopista Novia del Mediodia, Km 6½, La Lisa, Habana, Cuba.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez
authors.affiliation: Virology Department, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Pedro Kouri Institute of Tropical Medicine, Autopista Novia del Mediodia, Km 6½, La Lisa, Habana, Cuba.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Guzman
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism / Q000821:virology; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D003462:Cuba; D003715:Dengue / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003716:Dengue Virus / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000821:virology; D055815:Young Adult
chemical_list: D054405:Chemokine CCL3; D018946:Chemokine CCL5; D008024:Ligands; D012333:RNA, Messenger; D054389:Receptors, CCR1
keywords: Chemokines; Dengue; Gene expression; Immunopathogenesis