T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4 + T cells

Author:

Arbore Giuseppina1,West Erin E.2,Spolski Rosanne2,Robertson Avril A. B.3,Klos Andreas4,Rheinheimer Claudia4,Dutow Pavel4,Woodruff Trent M.3,Yu Zu Xi5,O’Neill Luke A.6,Coll Rebecca C.3,Sher Alan7,Leonard Warren J.2,Köhl Jörg89,Monk Pete10,Cooper Matthew A.3,Arno Matthew11,Afzali Behdad112,Lachmann Helen J.13,Cope Andrew P.14,Mayer-Barber Katrin D.15,Kemper Claudia12

Affiliation:

1. MRC Centre for Transplantation, Division of Transplant Immunology and Mucosal Biology, King’s College London, London SE1 9RT, UK.

2. Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.

3. Institute for Molecular Bioscience and School of Biomedical Sciences, University of Queensland, QLD 4072, Australia.

4. Institute for Medical Microbiology and Hospital Epidemiology, Medizinische Hochschule Hannover, 30625 Hannover, Germany.

5. Pathology Core, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.

6. School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.

7. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.

8. Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.

9. Division of Immunobiology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.

10. Department of Infection and Immunity, University of Sheffield, Sheffield S10 2RX, UK.

11. Genomics Centre, Faculty of Life Sciences and Medicine, King’s College London, London SE1 9NH, UK.

12. Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.

13. UK National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Campus, London NW3 2PF, UK.

14. Academic Department of Rheumatology, Division of Immunology, Infection and Inflammatory Diseases, King’s College London, London SE1 1UL, UK.

15. Laboratory of Clinical Infectious Diseases, Inflammation and Innate Immunity Unit, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.

Abstract

Innate immune crosstalk in T cells The classical view of immune activation is that innate immune cells, such as macrophages and dendritic cells, recognize invading microbes and then alert adaptive immune cells, such as T cells, to respond. Arbore et al. now show that innate and adaptive immunity converge in human and mouse T cells. Activated T cells express components of the complement cascade, which in turn leads to the assembly of NLRP3 inflammasomes—both critical components of innate immunity that help hosts detect and eliminate microbes. In T cells, complement and inflammasomes work together to push T cells to differentiate into a specialized subset of T cells important for eliminating intracellular bacteria. Science , this issue p. 10.1126/science.aad1210

Funder

MRC

Wellcome Trust Investigator Award

Wellcome Trust Intermediate Clinical Fellowship

British Heart Foundation

Science Foundation Ireland

Australia National Health

Medical Research Council

King’s College London

National Institute for Health Research (NIHR)

National Heart, Lung, and Blood Institute

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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