Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity

Autores
Morelli, María Paula; Martin, Candela; Pellegrini, Joaquín Miguel; Blanco, Federico Carlos; Bigi, Fabiana; Ciallella, Lorena; Musella, Rosa María; Rodriguez Mieres, Adriana; de Casado, Graciela C.; Palmero, Domingo; García, Verónica Edith
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient’s neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient’s neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB’s neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy.
Instituto de Biotecnología
Fil: Morelli, María Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Martin, Candela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Martin, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pellegrini, Joaquín Miguel. Parc Scientifique et Technologique de Luminy. Aix-Marseille Université. Centre National de la Recherche Scientifique (CNRS). Centre d'Immunologie de Marseille Luminy; Francia
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Bigi, Fabiana. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina
Fil: Ciallella, Lorena. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: Musella, Rosa María. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: Rodriguez Mieres, Adriana. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: de Casado, Graciela C. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: Palmero, Domingo. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
The Journal of Immunology 214 (6) : 1173-1186 (June 2025)
Materia
Cytokines
Neutrophils
Antiinflammatory Agents
Inflammation
Phenotypes
Disease Severity
Pathogenicity
Immune Response
Citoquinas
Neutrófilos
Tuberculosis
Antinflamatorios
Inflamación
Fenotipos
Gravedad de una Enfermedad
Mycobacterium tuberculosis
Patogenicidad
Respuesta Inmunológica
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/23105
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network_name_str INTA Digital (INTA)
spelling Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severityMorelli, María PaulaMartin, CandelaPellegrini, Joaquín MiguelBlanco, Federico CarlosBigi, FabianaCiallella, LorenaMusella, Rosa MaríaRodriguez Mieres, Adrianade Casado, Graciela C.Palmero, DomingoGarcía, Verónica EdithCytokinesNeutrophilsAntiinflammatory AgentsInflammationPhenotypesDisease SeverityPathogenicityImmune ResponseCitoquinasNeutrófilosTuberculosisAntinflamatoriosInflamaciónFenotiposGravedad de una EnfermedadMycobacterium tuberculosisPatogenicidadRespuesta InmunológicaNeutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient’s neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient’s neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB’s neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy.Instituto de BiotecnologíaFil: Morelli, María Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Martin, Candela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Martin, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pellegrini, Joaquín Miguel. Parc Scientifique et Technologique de Luminy. Aix-Marseille Université. Centre National de la Recherche Scientifique (CNRS). Centre d'Immunologie de Marseille Luminy; FranciaFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Bigi, Fabiana. Consejo Nacional de investigaciones Científicas y Técnicas; ArgentinaFil: Ciallella, Lorena. Hospital F. J. Muñiz. División Tisioneumonología; ArgentinaFil: Musella, Rosa María. Hospital F. J. Muñiz. División Tisioneumonología; ArgentinaFil: Rodriguez Mieres, Adriana. Hospital F. J. Muñiz. División Tisioneumonología; ArgentinaFil: de Casado, Graciela C. Hospital F. J. Muñiz. División Tisioneumonología; ArgentinaFil: Palmero, Domingo. Hospital F. J. Muñiz. División Tisioneumonología; ArgentinaFil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Association of Immunologists2025-07-21T14:27:30Z2025-07-21T14:27:30Z2025-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/23105https://academic.oup.com/jimmunol/article/214/6/1173/81064311550-6606https://doi.org/10.1093/jimmun/vkaf010The Journal of Immunology 214 (6) : 1173-1186 (June 2025)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2026-09-24T11:41:52Zoai:localhost:20.500.12123/23105instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-09-24 11:41:52.967INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity
title Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity
spellingShingle Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity
Morelli, María Paula
Cytokines
Neutrophils
Antiinflammatory Agents
Inflammation
Phenotypes
Disease Severity
Pathogenicity
Immune Response
Citoquinas
Neutrófilos
Tuberculosis
Antinflamatorios
Inflamación
Fenotipos
Gravedad de una Enfermedad
Mycobacterium tuberculosis
Patogenicidad
Respuesta Inmunológica
title_short Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity
title_full Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity
title_fullStr Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity
title_full_unstemmed Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity
title_sort Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity
dc.creator.none.fl_str_mv Morelli, María Paula
Martin, Candela
Pellegrini, Joaquín Miguel
Blanco, Federico Carlos
Bigi, Fabiana
Ciallella, Lorena
Musella, Rosa María
Rodriguez Mieres, Adriana
de Casado, Graciela C.
Palmero, Domingo
García, Verónica Edith
author Morelli, María Paula
author_facet Morelli, María Paula
Martin, Candela
Pellegrini, Joaquín Miguel
Blanco, Federico Carlos
Bigi, Fabiana
Ciallella, Lorena
Musella, Rosa María
Rodriguez Mieres, Adriana
de Casado, Graciela C.
Palmero, Domingo
García, Verónica Edith
author_role author
author2 Martin, Candela
Pellegrini, Joaquín Miguel
Blanco, Federico Carlos
Bigi, Fabiana
Ciallella, Lorena
Musella, Rosa María
Rodriguez Mieres, Adriana
de Casado, Graciela C.
Palmero, Domingo
García, Verónica Edith
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cytokines
Neutrophils
Antiinflammatory Agents
Inflammation
Phenotypes
Disease Severity
Pathogenicity
Immune Response
Citoquinas
Neutrófilos
Tuberculosis
Antinflamatorios
Inflamación
Fenotipos
Gravedad de una Enfermedad
Mycobacterium tuberculosis
Patogenicidad
Respuesta Inmunológica
topic Cytokines
Neutrophils
Antiinflammatory Agents
Inflammation
Phenotypes
Disease Severity
Pathogenicity
Immune Response
Citoquinas
Neutrófilos
Tuberculosis
Antinflamatorios
Inflamación
Fenotipos
Gravedad de una Enfermedad
Mycobacterium tuberculosis
Patogenicidad
Respuesta Inmunológica
dc.description.none.fl_txt_mv Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient’s neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient’s neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB’s neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy.
Instituto de Biotecnología
Fil: Morelli, María Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Martin, Candela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Martin, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pellegrini, Joaquín Miguel. Parc Scientifique et Technologique de Luminy. Aix-Marseille Université. Centre National de la Recherche Scientifique (CNRS). Centre d'Immunologie de Marseille Luminy; Francia
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Bigi, Fabiana. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina
Fil: Ciallella, Lorena. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: Musella, Rosa María. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: Rodriguez Mieres, Adriana. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: de Casado, Graciela C. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: Palmero, Domingo. Hospital F. J. Muñiz. División Tisioneumonología; Argentina
Fil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient’s neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient’s neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB’s neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy.
publishDate 2025
dc.date.none.fl_str_mv 2025-07-21T14:27:30Z
2025-07-21T14:27:30Z
2025-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/23105
https://academic.oup.com/jimmunol/article/214/6/1173/8106431
1550-6606
https://doi.org/10.1093/jimmun/vkaf010
url http://hdl.handle.net/20.500.12123/23105
https://academic.oup.com/jimmunol/article/214/6/1173/8106431
https://doi.org/10.1093/jimmun/vkaf010
identifier_str_mv 1550-6606
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
dc.source.none.fl_str_mv The Journal of Immunology 214 (6) : 1173-1186 (June 2025)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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