title: Integrated Transcriptomics Establish Macrophage Polarization Signatures and have Potential Applications for Clinical Health and Disease.
abstract: Growing evidence defines macrophages (Mφ) as plastic cells with wide-ranging states of activation and expression of different markers that are time and location dependent. Distinct from the simple M1/M2 dichotomy initially proposed, extensive diversity of macrophage phenotypes have been extensively demonstrated as characteristic features of monocyte-macrophage differentiation, highlighting the difficulty of defining complex profiles by a limited number of genes. Since the description of macrophage activation is currently contentious and confusing, the generation of a simple and reliable framework to categorize major Mφ phenotypes in the context of complex clinical conditions would be extremely relevant to unravel different roles played by these cells in pathophysiological scenarios. In the current study, we integrated transcriptome data using bioinformatics tools to generate two macrophage molecular signatures. We validated our signatures in in vitro experiments and in clinical samples. More importantly, we were able to attribute prognostic and predictive values to components of our signatures. Our study provides a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including dengue infections, asthma and sepsis resolution.
authors: Laboratory of Cellular Biochemistry, Department of Biochemistry, ICBS/UFRGS, 90035-003 Porto Alegre (RS), Brazil.|National Institutes of Science &Technology-Translational Medicine (INCT-TM), 90035-903 Porto Alegre (RS), Brazil.
authors: Matheus
authors: M
authors: Becker
authors: Laboratory of Cellular Biochemistry, Department of Biochemistry, ICBS/UFRGS, 90035-003 Porto Alegre (RS), Brazil.|National Institutes of Science &Technology-Translational Medicine (INCT-TM), 90035-903 Porto Alegre (RS), Brazil.
authors: Marco A
authors: MA
authors: De Bastiani
authors: Laboratory of Molecular Biology and Bioinformatics, Department of Biochemistry, ICBS/UFRGS, 90035-003 Porto Alegre (RS), Brazil.
authors: Mariana M
authors: MM
authors: Parisi
authors: Laboratory of Biochemistry and Cellular Biology of Lipids, Department of Biochemistry, ICBS/UFRGS, 90035-003 Porto Alegre (RS), Brazil.
authors: Fátima T C R
authors: FT
authors: Guma
authors: Laboratory of Cellular and Molecular Cardiology, IC/FUC, Porto Alegre, RS 90620-000, Brazil.
authors: Melissa M
authors: MM
authors: Markoski
authors: Laboratory of Bioinformatics, Professional and Technological Education Sector, Polytechnic Center, UFPR, 81531-970 Curitiba (PR), Brazil.
authors: Mauro A A
authors: MA
authors: Castro
authors: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis (IN), 46202, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (IN), 46202, USA.
authors: Mark H
authors: MH
authors: Kaplan
authors: Laboratory of Molecular Biology and Bioinformatics, Department of Biochemistry, ICBS/UFRGS, 90035-003 Porto Alegre (RS), Brazil.|Biomedical Research Institute, PUCRS, 90619-900, Porto Alegre (RS), Brazil.
authors: Florencia M
authors: FM
authors: Barbé-Tuana
authors: Laboratory of Cellular Biochemistry, Department of Biochemistry, ICBS/UFRGS, 90035-003 Porto Alegre (RS), Brazil.|National Institutes of Science &Technology-Translational Medicine (INCT-TM), 90035-903 Porto Alegre (RS), Brazil.
authors: Fábio
authors: F
authors: Klamt
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005240:Feasibility Studies; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D016215:Macrophage-Activating Factors / Q000276:immunology*; D008264:Macrophages / Q000145:classification* / Q000166:cytology / Q000276:immunology*; D018511:Systems Integration; D059467:Transcriptome
chemical_list: D016207:Cytokines; D016215:Macrophage-Activating Factors