title: Phenotypic and functional characteristics of HLA-DR+neutrophils in Brazilians with cutaneous leishmaniasis.
abstract: The protozoanLeishmania braziliensiscauses cutaneous leishmaniasis (CL) in endemic regions. In murine models, neutrophils (PMNs) are recruited to the site of infection soon after parasite inoculation. However, the roles of neutrophils during chronic infection and in human disease remain undefined. We hypothesized that neutrophils help maintain a systemic inflammatory state in subjects with CL. Lesion biopsies from all patients with CL tested contained neutrophils expressing HLA-DR, a molecule thought to be restricted to professional antigen-presenting cells. Although CL is a localized disease, a subset of patients with CL also had circulating neutrophils expressing HLA-DR and the costimulatory molecules CD80, CD86, and CD40. PMNs isolated from a low-density leukocyte blood fraction (LD-PMNs) contained a higher percentage of HLA-DR+PMNs than did normal-density PMNs. In vitro coculture experiments suggested LD-PMNs do not suppress T cell responses, differentiating them from MDSCs. Flow-sorted HLA-DR+PMNs morphologically resembled conventional PMNs, and they exhibited functional properties of PMNs. Compared with conventional PMNs, HLA-DR+PMNs showed increased activation, degranulation, DHR123 oxidation, and phagocytic capacity. A few HLA-DR+PMNs were observed in healthy subjects, and that proportion could be increased by incubation in either inflammatory cytokines or in plasma from a patient with CL. This was accompanied by an increase in PMNhladrb1mRNA, suggesting a possible connection between neutrophil "priming" and up-regulation of HLA-DR. These data suggest that PMNs that are primed for activation and that also express surface markers of antigen-presenting cells emerge in the circulation and infected tissue lesions of patients with CL.
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Davis
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Smriti
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.|Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais, INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil.
authors.forename: Jacilara
authors.initials: J
authors.lastname: Conceição
authors.affiliation: Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.|Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais, INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil.
authors.forename: Pedro
authors.initials: P
authors.lastname: Carneiro
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Novais
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Scott
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.affiliation: Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.|Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais, INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil.
authors.forename: Olivia
authors.initials: O
authors.lastname: Bacellar
authors.affiliation: Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.|Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais, INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil.|Fundação Gonçalo Muniz, Fiocruz-Bahia, Salvador, Bahia Brazil.
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Carvalho
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA; mary-wilson@uiowa.edu.|Departments of Internal Medicine and Microbiology, University of Iowa, Iowa City, Iowa, USA; and.|Research Service, Iowa City Veterans' Affairs Medical Center, Iowa City, Iowa, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wilson
mesh_terms: D000328:Adult; D001938:Brazil; D015550:Cell Degranulation; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D045142:Cross-Priming / Q000276:immunology; D003594:Cytoplasmic Granules / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D003911:Dextrans; D006684:HLA-DR Antigens
keywords: Leishmania; granulocyte; neutrophil