TY - JOUR
T1 - Antigen-specific B cells direct T follicular-like helper cells into lymphoid follicles to mediate Mycobacterium tuberculosis control
AU - Swanson, Rosemary V.
AU - Gupta, Ananya
AU - Foreman, Taylor W.
AU - Lu, Lan
AU - Choreno-Parra, Jose Alberto
AU - Mbandi, Stanley Kimbung
AU - Rosa, Bruce A.
AU - Akter, Sadia
AU - Das, Shibali
AU - Ahmed, Mushtaq
AU - Garcia-Hernandez, Maria de la Luz
AU - Singh, Dhiraj K.
AU - Esaulova, Ekaterina
AU - Artyomov, Maxim N.
AU - Gommerman, Jennifer
AU - Mehra, Smriti
AU - Zuniga, Joaquin
AU - Mitreva, Makedonka
AU - Scriba, Thomas J.
AU - Rangel-Moreno, Javier
AU - Kaushal, Deepak
AU - Khader, Shabaana A.
N1 - Funding Information:
This work was supported by Washington University in St. Louis and University of Chicago; NIH grants HL105427 and AI111914 to S.A.K.; AI123780 to S.A.K., D.K., T.S. and M.M.; AI134236 to S.A.K. and D.K.; R01AI134240, R01AI138587, P51OD011133, P51OD011104, U42OD010442, S10OD028732 and C06OD030079 to D.K.; and NIH grant AR069655 (Center for Musculoskeletal Research, University of Rochester). We thank M. Veschak, M. D. Dunlap and S. Thirunavukkarasu of Washington University of St. Louis, Department of Molecular Microbiology, and A. Seeger and L. Reese of University of Rochester, Department of Surgical Pathology for technical support and assistance.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/5
Y1 - 2023/5
N2 - Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause of death. Granuloma-associated lymphoid tissue (GrALT) correlates with protection during TB, but the mechanisms of protection are not understood. During TB, the transcription factor IRF4 in T cells but not B cells is required for the generation of the TH1 and TH17 subsets of helper T cells and follicular helper T (TFH)-like cellular responses. A population of IRF4+ T cells coexpress the transcription factor BCL6 during Mtb infection, and deletion of Bcl6 (Bcl6fl/fl) in CD4+ T cells (CD4cre) resulted in reduction of TFH-like cells, impaired localization within GrALT and increased Mtb burden. In contrast, the absence of germinal center B cells, MHC class II expression on B cells, antibody-producing plasma cells or interleukin-10-expressing B cells, did not increase Mtb susceptibility. Indeed, antigen-specific B cells enhance cytokine production and strategically localize TFH-like cells within GrALT via interactions between programmed cell death 1 (PD-1) and its ligand PD-L1 and mediate Mtb control in both mice and macaques.
AB - Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause of death. Granuloma-associated lymphoid tissue (GrALT) correlates with protection during TB, but the mechanisms of protection are not understood. During TB, the transcription factor IRF4 in T cells but not B cells is required for the generation of the TH1 and TH17 subsets of helper T cells and follicular helper T (TFH)-like cellular responses. A population of IRF4+ T cells coexpress the transcription factor BCL6 during Mtb infection, and deletion of Bcl6 (Bcl6fl/fl) in CD4+ T cells (CD4cre) resulted in reduction of TFH-like cells, impaired localization within GrALT and increased Mtb burden. In contrast, the absence of germinal center B cells, MHC class II expression on B cells, antibody-producing plasma cells or interleukin-10-expressing B cells, did not increase Mtb susceptibility. Indeed, antigen-specific B cells enhance cytokine production and strategically localize TFH-like cells within GrALT via interactions between programmed cell death 1 (PD-1) and its ligand PD-L1 and mediate Mtb control in both mice and macaques.
UR - http://www.scopus.com/inward/record.url?scp=85151469859&partnerID=8YFLogxK
U2 - 10.1038/s41590-023-01476-3
DO - 10.1038/s41590-023-01476-3
M3 - Article
C2 - 37012543
AN - SCOPUS:85151469859
SN - 1529-2908
VL - 24
SP - 855
EP - 868
JO - Nature immunology
JF - Nature immunology
IS - 5
ER -