Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.

The majority of Mycobacterium tuberculosis (Mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. However, the constituents of the effective "protective immunity" against tuberculosis responsible for containing most infections remain unknown. Evaluat...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Niaina Rakotosamimanana, T Mark Doherty, Lova H Andriamihantasoa, Vincent Richard, Brigitte Gicquel, Jean-Louis Soares, Alimuddin Zumla, Voahangy Rasolofo Razanamparany
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b92ba964a5140b983be7af4a446cfab
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6b92ba964a5140b983be7af4a446cfab
record_format	dspace
spelling	oai:doaj.org-article:6b92ba964a5140b983be7af4a446cfab2021-11-18T07:49:36ZExpression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.1932-620310.1371/journal.pone.0061154https://doaj.org/article/6b92ba964a5140b983be7af4a446cfab2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23593415/?tool=EBIhttps://doaj.org/toc/1932-6203The majority of Mycobacterium tuberculosis (Mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. However, the constituents of the effective "protective immunity" against tuberculosis responsible for containing most infections remain unknown. Evaluating gene transcriptional profiles in tuberculosis clinical cohorts is one approach to understanding the spectrum of tuberculosis progression. It is clear that apoptosis plays a role in the control of tuberculosis but the utility of apoptosis-related genes as surrogate markers of protection against tuberculosis has not been well investigated. To characterize potential surrogate markers that could discriminate different phases of the clinical tuberculosis spectrum, we investigated gene expression of several TNF-alpha dependent apoptotic genes (TNFR1, TNFR2, FLICE, FLIPs) by real-time RT-PCR of peripheral blood cells from cohorts of individuals with active tuberculosis or potential exposure to tuberculosis. Newly diagnosed tuberculosis patients (n = 23), their close household contacts (n = 80), and community controls (n = 46) were tested at intervals over a period of up to two years. Latent infection or previous Mtb contact was assessed by ELISPOT and TST and complete blood counts were performed during the follow up. Results showed significant upregulation of FLIPs expression by infected individuals regardless of clinical status at entry to the study. A higher percentage of lymphocytes was found in the infected household contacts that remained healthy. In contrast, in individuals with active TB, a significant upregulation of TNFR2 expression, a significantly higher percentage of monocytes and a significantly decreased lymphocyte count were seen, compared to subjects that remained healthy. Moreover, the household contacts who subsequently developed signs of TB also had a significantly high number of monocytes. These data suggest tuberculosis may be associated with decreased T-cell survival (perhaps due to apoptosis) while inhibition of apoptosis in monocytes could lead to a relative increase in these cells: a situation predicted to favour Mtb.Niaina RakotosamimananaT Mark DohertyLova H AndriamihantasoaVincent RichardBrigitte GicquelJean-Louis SoaresAlimuddin ZumlaVoahangy Rasolofo RazanamparanyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61154 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Niaina Rakotosamimanana T Mark Doherty Lova H Andriamihantasoa Vincent Richard Brigitte Gicquel Jean-Louis Soares Alimuddin Zumla Voahangy Rasolofo Razanamparany Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.
description	The majority of Mycobacterium tuberculosis (Mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. However, the constituents of the effective "protective immunity" against tuberculosis responsible for containing most infections remain unknown. Evaluating gene transcriptional profiles in tuberculosis clinical cohorts is one approach to understanding the spectrum of tuberculosis progression. It is clear that apoptosis plays a role in the control of tuberculosis but the utility of apoptosis-related genes as surrogate markers of protection against tuberculosis has not been well investigated. To characterize potential surrogate markers that could discriminate different phases of the clinical tuberculosis spectrum, we investigated gene expression of several TNF-alpha dependent apoptotic genes (TNFR1, TNFR2, FLICE, FLIPs) by real-time RT-PCR of peripheral blood cells from cohorts of individuals with active tuberculosis or potential exposure to tuberculosis. Newly diagnosed tuberculosis patients (n = 23), their close household contacts (n = 80), and community controls (n = 46) were tested at intervals over a period of up to two years. Latent infection or previous Mtb contact was assessed by ELISPOT and TST and complete blood counts were performed during the follow up. Results showed significant upregulation of FLIPs expression by infected individuals regardless of clinical status at entry to the study. A higher percentage of lymphocytes was found in the infected household contacts that remained healthy. In contrast, in individuals with active TB, a significant upregulation of TNFR2 expression, a significantly higher percentage of monocytes and a significantly decreased lymphocyte count were seen, compared to subjects that remained healthy. Moreover, the household contacts who subsequently developed signs of TB also had a significantly high number of monocytes. These data suggest tuberculosis may be associated with decreased T-cell survival (perhaps due to apoptosis) while inhibition of apoptosis in monocytes could lead to a relative increase in these cells: a situation predicted to favour Mtb.
format	article
author	Niaina Rakotosamimanana T Mark Doherty Lova H Andriamihantasoa Vincent Richard Brigitte Gicquel Jean-Louis Soares Alimuddin Zumla Voahangy Rasolofo Razanamparany
author_facet	Niaina Rakotosamimanana T Mark Doherty Lova H Andriamihantasoa Vincent Richard Brigitte Gicquel Jean-Louis Soares Alimuddin Zumla Voahangy Rasolofo Razanamparany
author_sort	Niaina Rakotosamimanana
title	Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.
title_short	Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.
title_full	Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.
title_fullStr	Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.
title_full_unstemmed	Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.
title_sort	expression of tnf-alpha-dependent apoptosis-related genes in the peripheral blood of malagasy subjects with tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6b92ba964a5140b983be7af4a446cfab
work_keys_str_mv	AT niainarakotosamimanana expressionoftnfalphadependentapoptosisrelatedgenesintheperipheralbloodofmalagasysubjectswithtuberculosis AT tmarkdoherty expressionoftnfalphadependentapoptosisrelatedgenesintheperipheralbloodofmalagasysubjectswithtuberculosis AT lovahandriamihantasoa expressionoftnfalphadependentapoptosisrelatedgenesintheperipheralbloodofmalagasysubjectswithtuberculosis AT vincentrichard expressionoftnfalphadependentapoptosisrelatedgenesintheperipheralbloodofmalagasysubjectswithtuberculosis AT brigittegicquel expressionoftnfalphadependentapoptosisrelatedgenesintheperipheralbloodofmalagasysubjectswithtuberculosis AT jeanlouissoares expressionoftnfalphadependentapoptosisrelatedgenesintheperipheralbloodofmalagasysubjectswithtuberculosis AT alimuddinzumla expressionoftnfalphadependentapoptosisrelatedgenesintheperipheralbloodofmalagasysubjectswithtuberculosis AT voahangyrasoloforazanamparany expressionoftnfalphadependentapoptosisrelatedgenesintheperipheralbloodofmalagasysubjectswithtuberculosis
_version_	1718422916394123264

Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis.

Ejemplares similares