Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils
Abstract Immune evasion strategies of Brucella, the etiologic agent of brucellosis, a global zoonosis, remain partially understood. The omentum, a tertiary lymphoid organ part of visceral adipose tissue, has never been explored as a Brucella reservoir. We report that B. abortus infects and replicate...
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2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55799-2 |
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| author | Joaquin M. Pellegrini Gabriela González-Espinoza Raheleh R. Shayan Lisiena Hysenaj Thomas Rouma Vilma Arce-Gorvel Hugues Lelouard Dimitri Popoff Yun Zhao Sean Hanniffy Amanda Castillo-Zeledón Maite Loperena-Barber Javier Celis-Gutierrez Cyrille Mionnet Mile Bosilkovski Javier Solera Eric Muraille Elías Barquero-Calvo Edgardo Moreno Raquel Conde-Álvarez Ignacio Moriyón Jean-Pierre Gorvel Sylvie Mémet |
| author_facet | Joaquin M. Pellegrini Gabriela González-Espinoza Raheleh R. Shayan Lisiena Hysenaj Thomas Rouma Vilma Arce-Gorvel Hugues Lelouard Dimitri Popoff Yun Zhao Sean Hanniffy Amanda Castillo-Zeledón Maite Loperena-Barber Javier Celis-Gutierrez Cyrille Mionnet Mile Bosilkovski Javier Solera Eric Muraille Elías Barquero-Calvo Edgardo Moreno Raquel Conde-Álvarez Ignacio Moriyón Jean-Pierre Gorvel Sylvie Mémet |
| author_sort | Joaquin M. Pellegrini |
| collection | DOAJ |
| description | Abstract Immune evasion strategies of Brucella, the etiologic agent of brucellosis, a global zoonosis, remain partially understood. The omentum, a tertiary lymphoid organ part of visceral adipose tissue, has never been explored as a Brucella reservoir. We report that B. abortus infects and replicates within murine omental macrophages. Throughout the chronic phase of infection, the omentum accumulates macrophages, monocytes and neutrophils. The maintenance of PD-L1+Sca-1+ macrophages, monocytes and neutrophils in the omentum depends on the wadC-encoded determinant of Brucella LPS. We demonstrate that PD-L1+Sca-1+ murine omental neutrophils produce high levels of IL-1RA leading to T cell hyporesponsiveness. These findings corroborate brucellosis patient analysis of whole blood displaying upregulation of PDL1 and Ly6E genes, and of serum exhibiting high levels of IL-1RA. Overall, the omentum, a reservoir for B. abortus, promotes bacterial persistence and causes CD4+ and CD8+ T cell immunosuppression by IL-1RA secreted by PD-L1+Sca-1+ neutrophils. |
| format | Article |
| id | doaj-art-8b32eea2b7ff42bcaf3cbd9d17a63666 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8b32eea2b7ff42bcaf3cbd9d17a636662025-08-20T02:48:12ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-024-55799-2Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophilsJoaquin M. Pellegrini0Gabriela González-Espinoza1Raheleh R. Shayan2Lisiena Hysenaj3Thomas Rouma4Vilma Arce-Gorvel5Hugues Lelouard6Dimitri Popoff7Yun Zhao8Sean Hanniffy9Amanda Castillo-Zeledón10Maite Loperena-Barber11Javier Celis-Gutierrez12Cyrille Mionnet13Mile Bosilkovski14Javier Solera15Eric Muraille16Elías Barquero-Calvo17Edgardo Moreno18Raquel Conde-Álvarez19Ignacio Moriyón20Jean-Pierre Gorvel21Sylvie Mémet22Aix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLUnité de Recherche en Biologie des Microorganismes (URBM)-Laboratoire d’Immunologie et de Microbiologie, NARILIS, University of NamurAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLUniversidad Nacional, Pathology Department, Escuela de Medicina VeterinariaUniversidad de Navarra, Instituto de Salud Tropical e Departamento de Microbiología y ParasitologíaAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLUniversity Clinic for Infectious Diseases and Febrile ConditionsHospital General Universitario, Facultad de Medicina, Universidad Castilla la Mancha AlbaceteUnité de Recherche en Biologie des Microorganismes (URBM)-Laboratoire d’Immunologie et de Microbiologie, NARILIS, University of NamurUniversidad Nacional, Pathology Department, Escuela de Medicina VeterinariaUniversidad Nacional, Pathology Department, Escuela de Medicina VeterinariaUniversidad de Navarra, Instituto de Salud Tropical e Departamento de Microbiología y ParasitologíaUniversidad de Navarra, Instituto de Salud Tropical e Departamento de Microbiología y ParasitologíaAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAbstract Immune evasion strategies of Brucella, the etiologic agent of brucellosis, a global zoonosis, remain partially understood. The omentum, a tertiary lymphoid organ part of visceral adipose tissue, has never been explored as a Brucella reservoir. We report that B. abortus infects and replicates within murine omental macrophages. Throughout the chronic phase of infection, the omentum accumulates macrophages, monocytes and neutrophils. The maintenance of PD-L1+Sca-1+ macrophages, monocytes and neutrophils in the omentum depends on the wadC-encoded determinant of Brucella LPS. We demonstrate that PD-L1+Sca-1+ murine omental neutrophils produce high levels of IL-1RA leading to T cell hyporesponsiveness. These findings corroborate brucellosis patient analysis of whole blood displaying upregulation of PDL1 and Ly6E genes, and of serum exhibiting high levels of IL-1RA. Overall, the omentum, a reservoir for B. abortus, promotes bacterial persistence and causes CD4+ and CD8+ T cell immunosuppression by IL-1RA secreted by PD-L1+Sca-1+ neutrophils.https://doi.org/10.1038/s41467-024-55799-2 |
| spellingShingle | Joaquin M. Pellegrini Gabriela González-Espinoza Raheleh R. Shayan Lisiena Hysenaj Thomas Rouma Vilma Arce-Gorvel Hugues Lelouard Dimitri Popoff Yun Zhao Sean Hanniffy Amanda Castillo-Zeledón Maite Loperena-Barber Javier Celis-Gutierrez Cyrille Mionnet Mile Bosilkovski Javier Solera Eric Muraille Elías Barquero-Calvo Edgardo Moreno Raquel Conde-Álvarez Ignacio Moriyón Jean-Pierre Gorvel Sylvie Mémet Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils Nature Communications |
| title | Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils |
| title_full | Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils |
| title_fullStr | Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils |
| title_full_unstemmed | Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils |
| title_short | Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils |
| title_sort | brucella abortus impairs t lymphocyte responsiveness by mobilizing il 1ra secreting omental neutrophils |
| url | https://doi.org/10.1038/s41467-024-55799-2 |
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