Gut Microbiota Regulates Mincle Mediated Activation of Lung Dendritic Cells to Protect Against .

Negi, Shikha and Pahari, Susanta and Bashir, Hilal and Agrewala, J N (2019) Gut Microbiota Regulates Mincle Mediated Activation of Lung Dendritic Cells to Protect Against . Frontiers in immunology, 10. p. 1142. ISSN 1664-3224

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Gut microbial components serve as ligand for various pattern 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 () 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 infection. We found that dysbiosis reduced the lung mincle expression with a concomitant increase in 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 survival. 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 upon mincle stimulation in microbiota depleted animals. Accordingly, supplementation with restored mincle expression on lung DCs along with anti- response. Our data demonstrate that gut microbiota is crucial to maintain DC-dependent lung immune response against , mediated by mincle. Abx interrupt this process to induce impaired T cell-response and increased susceptibility to .

Item Type: Article
Additional Information: Copyright of this article belongs to Frontiers Media S.A.
Uncontrolled Keywords: T cells; antibiotics; gut-lung axis; lung dendritic cells; mincle; tuberculosis
Subjects: Q Science > QR Microbiology > QR180 Immunology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 13 Aug 2019 14:42
Last Modified: 13 Aug 2019 14:42

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