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TB or not TB: Type 3 ILCs may decide

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Science Immunology  02 Aug 2019:
Vol. 4, Issue 38, eaay7254
DOI: 10.1126/sciimmunol.aay7254

Abstract

Mouse models are used to show that type 3 innate lymphoid cells provide early protection against Mtb infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) is the world’s leading infectious cause of death. Ardain et al. showed that numbers of blood innate lymphoid cells (ILCs)—including ILC3s, which induce Th17 responses—were lower in TB patients compared to controls. Numbers of ILC1s and ILC3s, but not ILC2s, increased after treatment, suggesting that Mtb bacteremia influences selective ILC accumulation. Using wild-type (WT) and knockout mouse models of Mtb infection, the authors found that the pulmonary accumulation of ILC3s was associated with alveolar macrophage accumulation and enhanced Mtb control. Th17 signaling deficient RORγt–/– mice demonstrated increased Mtb lung burden compared with WT mice. The authors discovered that the chemokine CXCL13, expressed in mouse and human lung following Mtb infection, decreased in the plasma of pulmonary TB patients upon treatment. Expression of the CXCL13 receptor CXCR5 was also increased in ILC3s from active TB patients, suggesting that the CXCL13-CXCR5 axis may support ILC3 activity after Mtb infection. As the CXCL13-CXCR5 axis also supports the formation of inducible bronchus-associated lymphoid tissue (iBALT), the group mechanistically investigated iBALT formation and pathogen clearance following Mtb infection in Rag2–/–IL2r-γ–/– mice (the latter which lack a significant pulmonary ILC response), with and without ILC subset add-back. Add-back of WT Mtb-infected ILC3s restored early Mtb clearance in Rag2–/–IL2r-γ–/– mice. These studies suggest that harnessing the effectiveness of ILC3s may be a novel avenue to elicit TB control through Th17 immunity.

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