Human IL‐6‐Producing B Cells Promote the Differentiation of Monocytes Toward an Anti‐Inflammatory CD16⁺CD163⁺CD206⁺PD‐L1⁺ Phenotype in Tuberculosis
The polarization of the monocyte/macrophage compartment toward an anti-inflammatory profile is considered detrimental in tuberculosis (TB), but the factors controlling M2 polarization in this context are still poorly understood. Here, we found that B cells promote the differentiation of human monocytes toward an M2-like activation program through a process primarily dependent on IL-6 and the activation of STAT3 signaling in monocytes. This confers monocytes with immunomodulatory properties characterized by a reduced ability to produce proinflammatory cytokines and to stimulate IFNγ secretion by allogeneic T cells. Our findings were validated using B cells from TB patients, which constitutively produce high levels of IL-6, underscoring the clinical relevance of our experimental observations. Collectively, our results indicate that human B-cell-derived IL-6 might impair TB immunity by driving monocyte polarization toward an anti-inflammatory phenotype.
Authors
- Denis Hudrisier (ORCID: https://orcid.org/0000-0002-3631-9561)
- Marı́a del Carmen Sasiain (ORCID: https://orcid.org/0000-0001-5616-7270)
- Luciana Balboa (ORCID: https://orcid.org/0000-0001-7045-3572)
- Alan Bénard (ORCID: https://orcid.org/0000-0002-7175-813X)
- Étienne Meunier (ORCID: https://orcid.org/0000-0002-3651-4877)
- Simon Fillatreau (ORCID: https://orcid.org/0000-0002-7730-9917)
- Olivier Neyrolles (ORCID: https://orcid.org/0000-0003-0047-5885)
- Maxime Caouaille (ORCID: https://orcid.org/0009-0006-9232-7773)
- Léa Ravon‐Katossky
Institutions
- Hôpital Necker-Enfants Malades (FR)
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Academia Nacional de Medicina (AR)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Inserm (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Université Paris Cité (FR)
- Institut Necker Enfants Malades (FR)
- Universitätsklinikum Erlangen (DE)
- Sorbonne Paris Cité (FR)
- Institut de Pharmacologie et de Biologie Structurale (FR)
Publication Details
- Journal
- European Journal of Immunology
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1002/eji.202451509
- Citations
- 2
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Fondation Bettencourt Schueller