Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis
Research output: Contribution to journal › Article
Colleges, School and Institutes
- Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
- Department of Tropical and Infectious Diseases, Institute of Primate Research, Nairobi, Kenya.
- Africa Health Research Institute, Durban, South Africa.
- Tulane National Primate Research Center, Covington, LA, USA.
- Tulane University Health Sciences, New Orleans, LA, USA.
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico.
- University College London
- Washington University School of Medicine
- University of Cape Town
- University of KwaZulu-Natal
- University of Rochester Medical Center
- South African Medical Research Council
- University of Alabama at Birmingham
Tuberculosis is the leading cause of death by an infectious disease worldwide1. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and restored upon treatment. Tuberculosis increased accumulation of ILC subsets in the human lung, coinciding with a robust transcriptional response to infection, including a role in orchestrating the recruitment of immune subsets. Using mouse models, we show that group 3 ILCs (ILC3s) accumulated rapidly in Mtb-infected lungs and coincided with the accumulation of alveolar macrophages. Notably, mice that lacked ILC3s exhibited a reduction in the accumulation of early alveolar macrophages and decreased Mtb control. We show that the C-X-C motif chemokine receptor 5 (CXCR5)-C-X-C motif chemokine ligand 13 (CXCL13) axis is involved in Mtb control, as infection upregulates CXCR5 on circulating ILC3s and increases plasma levels of its ligand, CXCL13, in humans. Moreover, interleukin-23-dependent expansion of ILC3s in mice and production of interleukin-17 and interleukin-22 were found to be critical inducers of lung CXCL13, early innate immunity and the formation of protective lymphoid follicles within granulomas. Thus, we demonstrate an early protective role for ILC3s in immunity to Mtb infection.
|Number of pages||5|
|Early online date||5 Jun 2019|
|Publication status||Published - 27 Jun 2019|