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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-1? 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.

SUBMITTER: Rocha BC

PROVIDER: S-EPMC4698035 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria.

Rocha Bruno Coelho BC Marques Pedro Elias PE Leoratti Fabiana Maria de Souza FMS Junqueira Caroline C Pereira Dhelio Batista DB Antonelli Lis Ribeiro do Valle LRDV Menezes Gustavo Batista GB Golenbock Douglas Taylor DT Gazzinelli Ricardo Tostes RT

Cell reports 20151217 12

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 ...[more]

PMID: 26711347

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Project description:IntroductionInterest in the potential role of low-density granulocytes (LDGs) in the development of autoimmune diseases has been renewed recently. Due to their pro-inflammatory action, more and more attention is paid to the role of LDGs, including those expressing the enzyme myeloperoxidase (MPO), in the development of autoimmune hepatitis (AIH). LDGs are actively involved in the formation of neutrophil extracellular traps (NETs). This phenomenon may favour the externalization of the autoantigen and lead to damage to internal organs, including the liver.AimThe main aim of the study was to assess the diagnostic usefulness of the LDG percentage, including the fraction showing MPO expression as markers of systemic inflammation in AIH.Materials and methodsThe study included a group of 25 patients with AIH and 20 healthy volunteers. Mononuclear cells, isolated from peripheral blood, were labelled with monoclonal antibodies conjugated to the appropriate fluorochromes (CD15-FITC, CD14-PE, CD10-PE-Cy5, MPO+) and then analyzed on a Navios Flow Cytometer (Beckman Coulter).ResultsPatients with AIH had a higher median percentage of LDG (1.2 vs. 0.1; p = 0.0001) and LDG expressing MPO (0.8 vs. 0.3; p = 0.0017) when compared to healthy volunteers. Moreover, the percentage of LDG was characterised by 100% of sensitivity and 55% of specificity (AUC = 0.84; p < 0.0001), while the percentage of LDG expressing MPO was 92% of sensitivity and 55% of specificity (AUC = 0.78; p = 0.0001) in the detection of AIH.ConclusionsAssessment of inflammatory markers, such as the percentage of LDG and the percentage of LDG expressing MPO, may be helpful in assessing the phenomenon of an increased systemic inflammatory response and in assessing liver fibrosis (LC, Liver cirrhosis), which is inherent in liver decompensation. Taking into account the above arguments, the assessment of the percentage of LDG, including LDG expressing MPO, may turn out to be a useful marker in the diagnosis of AIH.

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Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria.

Publications

Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria.

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