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Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction.
Vafadarnejad, Ehsan; Rizzo, Giuseppe; Krampert, Laura; Arampatzi, Panagiota; Arias-Loza, Anahi-Paula; Nazzal, Yara; Rizakou, Anna; Knochenhauer, Tim; Bandi, Sourish Reddy; Nugroho, Vallery Audy; Schulz, Dirk J J; Roesch, Melanie; Alayrac, Paul; Vilar, Jose; Silvestre, Jean-Sébastien; Zernecke, Alma; Saliba, Antoine-Emmanuel; Cochain, Clément.
Afiliación
  • Vafadarnejad E; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Wuerzburg, Germany (E.V., A.-E.S.).
  • Rizzo G; Comprehensive Heart Failure Center Wuerzburg (G.R., L.K., A.-P.A.-L., V.A.N., D.J.J.S., C.C.), University Hospital Wuerzburg, Germany.
  • Krampert L; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Arampatzi P; Comprehensive Heart Failure Center Wuerzburg (G.R., L.K., A.-P.A.-L., V.A.N., D.J.J.S., C.C.), University Hospital Wuerzburg, Germany.
  • Arias-Loza AP; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Nazzal Y; Core Unit Systems Medicine, University of Wuerzburg, Germany (P. Arampatzi).
  • Rizakou A; Comprehensive Heart Failure Center Wuerzburg (G.R., L.K., A.-P.A.-L., V.A.N., D.J.J.S., C.C.), University Hospital Wuerzburg, Germany.
  • Knochenhauer T; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Bandi SR; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Nugroho VA; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Schulz DJJ; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Roesch M; Comprehensive Heart Failure Center Wuerzburg (G.R., L.K., A.-P.A.-L., V.A.N., D.J.J.S., C.C.), University Hospital Wuerzburg, Germany.
  • Alayrac P; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Vilar J; Comprehensive Heart Failure Center Wuerzburg (G.R., L.K., A.-P.A.-L., V.A.N., D.J.J.S., C.C.), University Hospital Wuerzburg, Germany.
  • Silvestre JS; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Zernecke A; Institute of Experimental Biomedicine (G.R., L.K.,Y.N., A.R., T.K., S.R.B., V.A.N., D.J.J.S., M.R., A.Z., C.C.), University Hospital Wuerzburg, Germany.
  • Saliba AE; Université de Paris, PARCC, INSERM, F-75015 Paris, France (P. Alayrac, J.V., J.-S.S.).
  • Cochain C; Université de Paris, PARCC, INSERM, F-75015 Paris, France (P. Alayrac, J.V., J.-S.S.).
Circ Res ; 127(9): e232-e249, 2020 10 09.
Article en En | MEDLINE | ID: mdl-32811295
ABSTRACT
RATIONALE After myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they promote both tissue healing and damage.

OBJECTIVE:

To characterize the dynamics of circulating and cardiac neutrophil diversity after infarction. METHODS AND

RESULTS:

We employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, cardiac Ly6G+ (lymphocyte antigen 6G) neutrophils could be delineated into 6 distinct clusters with specific time-dependent patterning and proportions. At day 1, neutrophils were characterized by a gene expression profile proximal to bone marrow neutrophils (Cd177, Lcn2, Fpr1), and putative activity of transcriptional regulators involved in hypoxic response (Hif1a) and emergency granulopoiesis (Cebpb). At 3 and 5 days, 2 major subsets of Siglecfhi (enriched for eg, Icam1 and Tnf) and Siglecflow (Slpi, Ifitm1) neutrophils were found. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis in blood and heart revealed that while circulating neutrophils undergo a process of aging characterized by loss of surface CD62L and upregulation of Cxcr4, heart infiltrating neutrophils acquired a unique SiglecFhi signature. SiglecFhi neutrophils were absent from the bone marrow and spleen, indicating local acquisition of the SiglecFhi signature. Reducing the influx of blood neutrophils by anti-Ly6G treatment increased proportions of cardiac SiglecFhi neutrophils, suggesting accumulation of locally aged neutrophils. Computational analysis of ligand/receptor interactions revealed putative pathways mediating neutrophil to macrophage communication in the myocardium. Finally, SiglecFhi neutrophils were also found in atherosclerotic vessels, revealing that they arise across distinct contexts of cardiovascular inflammation.

CONCLUSIONS:

Altogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse blood and ischemic heart at the single-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecFhi signature.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Infiltración Neutrófila / Infarto del Miocardio / Neutrófilos Límite: Animals Idioma: En Revista: Circ Res Año: 2020 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Asunto principal: Infiltración Neutrófila / Infarto del Miocardio / Neutrófilos Límite: Animals Idioma: En Revista: Circ Res Año: 2020 Tipo del documento: Article