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Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection

To determine the mechanisms that mediate resistance to Mycobacterium tuberculosis (M. tuberculosis) infection in household contacts (HHCs) of patients with tuberculosis (TB), we followed 452 latent TB infection–negative (LTBI(–)) HHCs for 2 years. Those who remained LTBI(–) throughout the study were...

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Autores principales: Tripathi, Deepak, Devalraju, Kamakshi Prudhula, Neela, Venkata Sanjeev Kumar, Mukherjee, Tanmoy, Paidipally, Padmaja, Radhakrishnan, Rajesh Kumar, Dozmorov, Igor, Vankayalapati, Abhinav, Ansari, Mohammad Soheb, Mallidi, Varalakshmi, Bogam, Anvesh Kumar, Singh, Karan P., Samten, Buka, Valluri, Vijaya Lakshmi, Vankayalapati, Ramakrishna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746823/
https://www.ncbi.nlm.nih.gov/pubmed/36509283
http://dx.doi.org/10.1172/jci.insight.152357
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author Tripathi, Deepak
Devalraju, Kamakshi Prudhula
Neela, Venkata Sanjeev Kumar
Mukherjee, Tanmoy
Paidipally, Padmaja
Radhakrishnan, Rajesh Kumar
Dozmorov, Igor
Vankayalapati, Abhinav
Ansari, Mohammad Soheb
Mallidi, Varalakshmi
Bogam, Anvesh Kumar
Singh, Karan P.
Samten, Buka
Valluri, Vijaya Lakshmi
Vankayalapati, Ramakrishna
author_facet Tripathi, Deepak
Devalraju, Kamakshi Prudhula
Neela, Venkata Sanjeev Kumar
Mukherjee, Tanmoy
Paidipally, Padmaja
Radhakrishnan, Rajesh Kumar
Dozmorov, Igor
Vankayalapati, Abhinav
Ansari, Mohammad Soheb
Mallidi, Varalakshmi
Bogam, Anvesh Kumar
Singh, Karan P.
Samten, Buka
Valluri, Vijaya Lakshmi
Vankayalapati, Ramakrishna
author_sort Tripathi, Deepak
collection PubMed
description To determine the mechanisms that mediate resistance to Mycobacterium tuberculosis (M. tuberculosis) infection in household contacts (HHCs) of patients with tuberculosis (TB), we followed 452 latent TB infection–negative (LTBI(–)) HHCs for 2 years. Those who remained LTBI(–) throughout the study were identified as nonconverters. At baseline, nonconverters had a higher percentage of CD14(+) and CD3(–)CD56(+)CD27(+)CCR7(+) memory-like natural killer (NK) cells. Using a whole-transcriptome and metabolomic approach, we identified deoxycorticosterone acetate as a metabolite with elevated concentrations in the plasma of nonconverters, and further studies showed that this metabolite enhanced glycolytic ATP flux in macrophages and restricted M. tuberculosis growth by enhancing antimicrobial peptide production through the expression of the surface receptor sialic acid binding Ig-like lectin–14. Another metabolite, 4-hydroxypyridine, from the plasma of nonconverters significantly enhanced the expansion of memory-like NK cells. Our findings demonstrate that increased levels of specific metabolites can regulate innate resistance against M. tuberculosis infection in HHCs of patients with TB who never develop LTBI or active TB.
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spelling pubmed-97468232022-12-15 Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection Tripathi, Deepak Devalraju, Kamakshi Prudhula Neela, Venkata Sanjeev Kumar Mukherjee, Tanmoy Paidipally, Padmaja Radhakrishnan, Rajesh Kumar Dozmorov, Igor Vankayalapati, Abhinav Ansari, Mohammad Soheb Mallidi, Varalakshmi Bogam, Anvesh Kumar Singh, Karan P. Samten, Buka Valluri, Vijaya Lakshmi Vankayalapati, Ramakrishna JCI Insight Research Article To determine the mechanisms that mediate resistance to Mycobacterium tuberculosis (M. tuberculosis) infection in household contacts (HHCs) of patients with tuberculosis (TB), we followed 452 latent TB infection–negative (LTBI(–)) HHCs for 2 years. Those who remained LTBI(–) throughout the study were identified as nonconverters. At baseline, nonconverters had a higher percentage of CD14(+) and CD3(–)CD56(+)CD27(+)CCR7(+) memory-like natural killer (NK) cells. Using a whole-transcriptome and metabolomic approach, we identified deoxycorticosterone acetate as a metabolite with elevated concentrations in the plasma of nonconverters, and further studies showed that this metabolite enhanced glycolytic ATP flux in macrophages and restricted M. tuberculosis growth by enhancing antimicrobial peptide production through the expression of the surface receptor sialic acid binding Ig-like lectin–14. Another metabolite, 4-hydroxypyridine, from the plasma of nonconverters significantly enhanced the expansion of memory-like NK cells. Our findings demonstrate that increased levels of specific metabolites can regulate innate resistance against M. tuberculosis infection in HHCs of patients with TB who never develop LTBI or active TB. American Society for Clinical Investigation 2022-11-22 /pmc/articles/PMC9746823/ /pubmed/36509283 http://dx.doi.org/10.1172/jci.insight.152357 Text en © 2022 Tripathi et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Tripathi, Deepak
Devalraju, Kamakshi Prudhula
Neela, Venkata Sanjeev Kumar
Mukherjee, Tanmoy
Paidipally, Padmaja
Radhakrishnan, Rajesh Kumar
Dozmorov, Igor
Vankayalapati, Abhinav
Ansari, Mohammad Soheb
Mallidi, Varalakshmi
Bogam, Anvesh Kumar
Singh, Karan P.
Samten, Buka
Valluri, Vijaya Lakshmi
Vankayalapati, Ramakrishna
Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection
title Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection
title_full Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection
title_fullStr Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection
title_full_unstemmed Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection
title_short Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection
title_sort metabolites enhance innate resistance to human mycobacterium tuberculosis infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746823/
https://www.ncbi.nlm.nih.gov/pubmed/36509283
http://dx.doi.org/10.1172/jci.insight.152357
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