PMID- 31231363
OWN - NLM
STAT- MEDLINE
DCOM- 20200817
LR  - 20200817
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Gut Microbiota Regulates Mincle Mediated Activation of Lung Dendritic Cells to 
      Protect Against Mycobacterium tuberculosis.
PG  - 1142
LID - 10.3389/fimmu.2019.01142 [doi]
LID - 1142
AB  - 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 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 naive 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.
FAU - Negi, Shikha
AU  - Negi S
AD  - Immunology Division, CSIR-Institute of Microbial Technology, Chandigarh, India.
FAU - Pahari, Susanta
AU  - Pahari S
AD  - Immunology Division, CSIR-Institute of Microbial Technology, Chandigarh, India.
AD  - Immunology Division, Texas Biomedical Research Institute, San Antonio, TX, United 
      States.
FAU - Bashir, Hilal
AU  - Bashir H
AD  - Immunology Division, CSIR-Institute of Microbial Technology, Chandigarh, India.
FAU - Agrewala, Javed N
AU  - Agrewala JN
AD  - Immunology Division, CSIR-Institute of Microbial Technology, Chandigarh, India.
AD  - Center for Biomedical Engineering, Indian Institute of Technology, Rupnagar, 
      India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190528
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Clecsf8 protein, mouse)
RN  - 0 (Glycolipids)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Pattern Recognition)
RN  - 0 (trehalose 6,6'-dibehenate)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/administration & dosage/pharmacology
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - Dendritic Cells/*immunology
MH  - Dysbiosis/drug therapy/immunology/microbiology
MH  - Gastrointestinal Microbiome/*immunology
MH  - Glycolipids/administration & dosage/pharmacology
MH  - Immunity, Innate/drug effects/immunology
MH  - Lactobacillus/immunology/physiology
MH  - Lectins, C-Type/genetics/*immunology/metabolism
MH  - Lung/*immunology
MH  - Macrophages/immunology/metabolism
MH  - Membrane Proteins/genetics/*immunology/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mycobacterium tuberculosis/*immunology/physiology
MH  - Receptors, Pattern Recognition/immunology/metabolism
MH  - Tuberculosis/drug therapy/*immunology/microbiology
PMC - PMC6558411
OTO - NOTNLM
OT  - T cells
OT  - antibiotics
OT  - gut-lung axis
OT  - lung dendritic cells
OT  - mincle
OT  - tuberculosis
EDAT- 2019/06/25 06:00
MHDA- 2020/08/18 06:00
PMCR- 2019/01/01
CRDT- 2019/06/25 06:00
PHST- 2018/11/21 00:00 [received]
PHST- 2019/05/07 00:00 [accepted]
PHST- 2019/06/25 06:00 [entrez]
PHST- 2019/06/25 06:00 [pubmed]
PHST- 2020/08/18 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.01142 [doi]
PST - epublish
SO  - Front Immunol. 2019 May 28;10:1142. doi: 10.3389/fimmu.2019.01142. eCollection 
      2019.