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

Autores
Morelli, María Paula; Martín, Candela; Pellegrini, Joaquín Miguel; Blanco, Federico Carlos; Bigi, Fabiana; Ciallella, Lorena María Cecilia; Musella, Rosa María; Rodriguez Mieres, Adriana; de Casado, Graciela C.; Palmero, Domingo Juan; 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.
Fil: Morelli, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Martín, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Pellegrini, Joaquín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Ciallella, Lorena María Cecilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Rodriguez Mieres, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: de Casado, Graciela C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Palmero, Domingo Juan. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
BACTERIAL INFECTION
CELL SURFACE MOLECULES
CYTOKINES
NEUTROPHILS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/292060
Acceder
id CONICETDig_319168b1426f20bd9664acec09127ac4
oai_identifier_str oai:ri.conicet.gov.ar:11336/292060
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severityMorelli, María PaulaMartín, CandelaPellegrini, Joaquín MiguelBlanco, Federico CarlosBigi, FabianaCiallella, Lorena María CeciliaMusella, Rosa MaríaRodriguez Mieres, Adrianade Casado, Graciela C.Palmero, Domingo JuanGarcía, Verónica EdithBACTERIAL INFECTIONCELL SURFACE MOLECULESCYTOKINESNEUTROPHILShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Neutrophils 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.Fil: Morelli, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Martín, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pellegrini, Joaquín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Ciallella, Lorena María Cecilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Rodriguez Mieres, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: de Casado, Graciela C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Palmero, Domingo Juan. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaAmerican Association of Immunologists2025-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/292060Morelli, María Paula; Martín, Candela; Pellegrini, Joaquín Miguel; Blanco, Federico Carlos; Bigi, Fabiana; et al.; Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity; American Association of Immunologists; Journal of Immunology; 214; 6; 4-2025; 1173-11860022-1767CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jimmunol/advance-article/doi/10.1093/jimmun/vkaf010/8106431info:eu-repo/semantics/altIdentifier/doi/10.1093/jimmun/vkaf010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:33:04Zoai:ri.conicet.gov.ar:11336/292060instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 14:33:04.849CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
BACTERIAL INFECTION
CELL SURFACE MOLECULES
CYTOKINES
NEUTROPHILS
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
Martín, Candela
Pellegrini, Joaquín Miguel
Blanco, Federico Carlos
Bigi, Fabiana
Ciallella, Lorena María Cecilia
Musella, Rosa María
Rodriguez Mieres, Adriana
de Casado, Graciela C.
Palmero, Domingo Juan
García, Verónica Edith
author Morelli, María Paula
author_facet Morelli, María Paula
Martín, Candela
Pellegrini, Joaquín Miguel
Blanco, Federico Carlos
Bigi, Fabiana
Ciallella, Lorena María Cecilia
Musella, Rosa María
Rodriguez Mieres, Adriana
de Casado, Graciela C.
Palmero, Domingo Juan
García, Verónica Edith
author_role author
author2 Martín, Candela
Pellegrini, Joaquín Miguel
Blanco, Federico Carlos
Bigi, Fabiana
Ciallella, Lorena María Cecilia
Musella, Rosa María
Rodriguez Mieres, Adriana
de Casado, Graciela C.
Palmero, Domingo Juan
García, Verónica Edith
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BACTERIAL INFECTION
CELL SURFACE MOLECULES
CYTOKINES
NEUTROPHILS
topic BACTERIAL INFECTION
CELL SURFACE MOLECULES
CYTOKINES
NEUTROPHILS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
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.
Fil: Morelli, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Martín, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Pellegrini, Joaquín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Ciallella, Lorena María Cecilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Rodriguez Mieres, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: de Casado, Graciela C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Palmero, Domingo Juan. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; 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 2025-04
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/11336/292060
Morelli, María Paula; Martín, Candela; Pellegrini, Joaquín Miguel; Blanco, Federico Carlos; Bigi, Fabiana; et al.; Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity; American Association of Immunologists; Journal of Immunology; 214; 6; 4-2025; 1173-1186
0022-1767
CONICET Digital
CONICET
url http://hdl.handle.net/11336/292060
identifier_str_mv Morelli, María Paula; Martín, Candela; Pellegrini, Joaquín Miguel; Blanco, Federico Carlos; Bigi, Fabiana; et al.; Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity; American Association of Immunologists; Journal of Immunology; 214; 6; 4-2025; 1173-1186
0022-1767
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jimmunol/advance-article/doi/10.1093/jimmun/vkaf010/8106431
info:eu-repo/semantics/altIdentifier/doi/10.1093/jimmun/vkaf010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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 reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.24418

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