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Front. Immunol. | doi: 10.3389/fimmu.2019.01142

Gut microbiota regulates mincle mediated activation of lung dendritic cells to protect against Mycobacterium tuberculosis

  • 1Institute of Microbial Technology (CSIR), India

Gut microbial components serve as ligand for various pathogen recognition receptors (PRRs) present on immune cells and thereby regulates host immunity. Dendritic cells (DCs) are highly specialized innate cells involved in immune response to Mycobacterium tuberculosis (Mtb) infection. The gut-lung axis is a potential therapeutic target in tuberculosis; however, understanding of the innate immune mechanism underlying the interaction of gut microbiota and lung still remains obscure. We investigated if antibiotics (Abx) induced gut dysbiosis is able to affect the activation of innate receptor, macrophage inducible C-type lectin (mincle) in lungs during Mtb infection. We found that dysbiosis reduced the lung mincle expression with a concomitant increase in Mtb survival. Further, Abx diminished the effector and memory T cell population, while elevating frequency of regulatory T cells (Tregs) in the lungs. Here, we show that dysbiotic mice exhibited low mincle expression on lung DCs. These DCs with impaired phenotype and functions had reduced ability to activate naïve CD4 T cells, and thus unable to restrict Mtb survival. In vivo administration of trehalose-6,6-dibehenate (TDB: mincle ligand) efficiently rescued this immune defect by enhancing lung DCs function and subsequent T cell response. Further, gut microbial profiling revealed augmentation of Lactobacillus upon mincle stimulation in microbiota depleted animals. Accordingly, supplementation with Lactobacillus restored mincle expression on lung DCs along with anti-Mtb response. Our data demonstrate that gut microbiota is crucial to maintain DC-dependent lung immune response against Mtb, mediated by mincle. Abx interrupt this process to induce impaired T cell-response and increased susceptibility to Mtb.

Keywords: Gut-Lung Axis, antibiotics, Mincle, T cells, lung dendritic cells

Received: 21 Nov 2018; Accepted: 07 May 2019.

Edited by:

Ed C. Lavelle, Trinity College Dublin, Ireland

Reviewed by:

Diane Bimczok, Montana State University, United States
Nathalie Winter, Institut National de la Recherche Agronomique (INRA), France  

Copyright: © 2019 Negi, Pahari, Bashir and Agrewala. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Javed N. Agrewala, Institute of Microbial Technology (CSIR), Chandigarh, India, javed@imtech.res.in