title: Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria.
abstract: Neutrophils are the most abundant leukocyte population in the bloodstream, the primary compartment of Plasmodium sp. infection. However, the role of these polymorphonuclear cells in mediating either the resistance or the pathogenesis of malaria is poorly understood. We report that circulating neutrophils from malaria patients are highly activated, as indicated by a strong type I interferon transcriptional signature, increased expression of surface activation markers, enhanced release of reactive oxygen species and myeloperoxidase, and a high frequency of low-density granulocytes. The activation of neutrophils was associated with increased levels of serum alanine and aspartate aminotransferases, indicating liver damage. In a rodent malaria model, we observed intense recruitment of neutrophils to liver sinusoids. Neutrophil migration and IL-1β and chemokine expression as well as liver damage were all dependent on type I interferon signaling. The data suggest that type I interferon signaling has a central role in neutrophil activation and malaria pathogenesis.
authors.affiliation: Departamento de Bioquímica e Imunologia, ICB; Universidade Federal de Minas Gerais; Belo Horizonte, MG, 31270-901; Brazil.|Department of Medicine; University of Massachusetts Medical School; Worcester, MA, 01605; United States of America.|Centro de Pesquisas Rene Rachou, FIOCRUZ-MG; Belo Horizonte, MG, 30190-002; Brazil.
authors.forename: Bruno Coelho
authors.initials: BC
authors.lastname: Rocha
authors.affiliation: Departamento de Morfologia, ICB; Universidade Federal de Minas Gerais; Belo Horizonte, MG, 31270-901; Brazil.
authors.forename: Pedro Elias
authors.initials: PE
authors.lastname: Marques
authors.affiliation: Centro de Pesquisas Rene Rachou, FIOCRUZ-MG; Belo Horizonte, MG, 30190-002; Brazil.
authors.forename: Fabiana Maria de Souza
authors.initials: FMS
authors.lastname: Leoratti
authors.affiliation: Centro de Pesquisas Rene Rachou, FIOCRUZ-MG; Belo Horizonte, MG, 30190-002; Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Junqueira
authors.affiliation: Centro de Pesquisas em Medicina Tropical, FIOCRUZ-RO; Porto Velho, RO, 76812-329; Brazil.
authors.forename: Dhelio Batista
authors.initials: DB
authors.lastname: Pereira
authors.affiliation: Centro de Pesquisas Rene Rachou, FIOCRUZ-MG; Belo Horizonte, MG, 30190-002; Brazil.
authors.forename: Lis Ribeiro do Valle
authors.initials: LRDV
authors.lastname: Antonelli
authors.affiliation: Departamento de Morfologia, ICB; Universidade Federal de Minas Gerais; Belo Horizonte, MG, 31270-901; Brazil.
authors.forename: Gustavo Batista
authors.initials: GB
authors.lastname: Menezes
authors.affiliation: Department of Medicine; University of Massachusetts Medical School; Worcester, MA, 01605; United States of America.
authors.forename: Douglas Taylor
authors.initials: DT
authors.lastname: Golenbock
authors.affiliation: Departamento de Bioquímica e Imunologia, ICB; Universidade Federal de Minas Gerais; Belo Horizonte, MG, 31270-901; Brazil.|Department of Medicine; University of Massachusetts Medical School; Worcester, MA, 01605; United States of America.|Centro de Pesquisas Rene Rachou, FIOCRUZ-MG; Belo Horizonte, MG, 30190-002; Brazil.
authors.forename: Ricardo Tostes
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000818:Animals; D006098:Granulocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008288:Malaria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D007370:Interferon Type I