title: CD163L1 and CLEC5A discriminate subsets of human resident and inflammatory macrophages in vivo.
abstract: Macrophages (Mϕ) can be differentiated and polarized in vitro from human CD14(+) monocytes under the influence of GM-CSF (GM-Mϕ) and M-CSF (M-Mϕ). GM-Mϕs are proinflammatory and M-Mϕs have an anti-inflammatory phenotype. We found selective expression of the lectin C-type lectin domain family 5 member A (CLEC5A) transcripts in GM-Mϕs and the scavenger receptor CD163 molecule-like 1 (CD163L1) in M-Mϕs by microarray assay. In vitro, CD163L1 expression was induced by IL-10 and M-CSF and CLEC5A by inflammatory cytokines and cell adherence. In secondary lymphoid organs, their respective expression was restricted to CD68(+)/CD163(+) Mϕs that preferentially produced either TNF (CLEC5A(+)) or IL-10 (CD163L1(+)). Mϕs from healthy liver and colon tissue were mostly CD163L1(+), and CLEC5A(+) cells were scarce. In contrast, CLEC5A(+) Mϕs were abundant in the intestinal lamina propria from patients with inflammatory bowel disease (IBD), with higher numbers of CLEC5A(+)CD163L1(+) found compared with those in secondary lymphoid organs. CLEC5A(+) cells were CD14(+)CD209(-)CD11b(+)CD11c(+)TNF(+)IL-10(+), and single positive CD163L1(+) cells were CD14(-)CD209(+)CD11b(-)CD11c(-)TNF(-)IL-10(+) in healthy donors and had lost the ability to produce IL-10 and to express CD209 in those with IBD. In melanomas, CLEC5A(+) tumor-associated Mϕs (TAMs) were not detected in 42% of the cases evaluated, but CD163L1(+) TAMs were found in 100%. Similar to IBD, CD163L1(+) TAMs expressed high levels of CD209 and produced significant amounts of IL-10, and CLEC5A(+) TAMs were CD14(hi) and produced enhanced levels of TNF in metastases. Overall, these results suggest that CD163L1 expression is associated with tissue-resident Mϕs with an anti-inflammatory or anergic phenotype and that CLEC5A(+) Mϕs exhibit TNF-producing ability and might display a proinflammatory effect.
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: Érika
authors: É
authors: González-Domínguez
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: Rafael
authors: R
authors: Samaniego
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: José Luis
authors: JL
authors: Flores-Sevilla
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: Salvador F
authors: SF
authors: Campos-Campos
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: Guillermo
authors: G
authors: Gómez-Campos
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: Azucena
authors: A
authors: Salas
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: Victoria
authors: V
authors: Campos-Peña
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: Ángel L
authors: ÁL
authors: Corbí
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain.
authors: Paloma
authors: P
authors: Sánchez-Mateos
authors: *Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria "Gregorio Marañón," Madrid, Spain; Servicio de Cirugía and Servicio de Patología, Hospital de Especialidades "Dr. Antonio Fraga Mouret," Centro Médico Nacional La Raza (IMSS), Mexico City, Mexico; Institut d'Investigacions Biomèdiques "August Pi i Sunyer," Barcelona, Spain; Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "Manuel Velazco Suárez," Mexico City, Mexico; Laboratory of Myeloid Cells, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and **Department of Immunology, Hospital "Gregorio Marañón," Health Research Institute, Complutense University School of Medicine, Madrid, Spain csanchez@cinvestav.mx.
authors: Carmen
authors: C
authors: Sánchez-Torres
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000032:analysis / Q000096:biosynthesis*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D018613:Microscopy, Confocal; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis*; D051116:Receptors, Scavenger; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C417665:CD163L1 protein, human; C509771:CLEC5A protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger
keywords: cancer; inflammation; myeloid subsets; polarization