CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.

<h4>Background</h4>Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculo...

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Autores principales:	Zahra Hasan, Jacqueline M Cliff, Hazel M Dockrell, Bushra Jamil, Muhammad Irfan, Mussarat Ashraf, Rabia Hussain
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/124c03e80c094ada91d79ccb54f1e17a
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spelling	oai:doaj.org-article:124c03e80c094ada91d79ccb54f1e17a2021-11-25T06:27:06ZCCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.1932-620310.1371/journal.pone.0008459https://doaj.org/article/124c03e80c094ada91d79ccb54f1e17a2009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20041183/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity.<h4>Methodology</h4>We investigated live M. tuberculosis- and M. bovis BCG-induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, n = 16). Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2, TNFalpha, CCL3 and CXCL8 were determined.<h4>Results</h4>M. tuberculosis- and BCG-induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01) as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p = 0.023), while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005) patients. M. tuberculosis-induced IFNgamma was greater in L-ETB than PTB (p = 0.04), while BCG-induced IFNgamma was greater in L-ETB as compared with D-ETB patients (p = 0.036). TNFalpha mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p = 0.02) and BCG (p = 0.03). Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups.<h4>Conclusions</h4>The increased CCL2 and TNFalpha in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease.Zahra HasanJacqueline M CliffHazel M DockrellBushra JamilMuhammad IrfanMussarat AshrafRabia HussainPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 12, p e8459 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zahra Hasan Jacqueline M Cliff Hazel M Dockrell Bushra Jamil Muhammad Irfan Mussarat Ashraf Rabia Hussain CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.
description	<h4>Background</h4>Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity.<h4>Methodology</h4>We investigated live M. tuberculosis- and M. bovis BCG-induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, n = 16). Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2, TNFalpha, CCL3 and CXCL8 were determined.<h4>Results</h4>M. tuberculosis- and BCG-induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01) as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p = 0.023), while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005) patients. M. tuberculosis-induced IFNgamma was greater in L-ETB than PTB (p = 0.04), while BCG-induced IFNgamma was greater in L-ETB as compared with D-ETB patients (p = 0.036). TNFalpha mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p = 0.02) and BCG (p = 0.03). Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups.<h4>Conclusions</h4>The increased CCL2 and TNFalpha in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease.
format	article
author	Zahra Hasan Jacqueline M Cliff Hazel M Dockrell Bushra Jamil Muhammad Irfan Mussarat Ashraf Rabia Hussain
author_facet	Zahra Hasan Jacqueline M Cliff Hazel M Dockrell Bushra Jamil Muhammad Irfan Mussarat Ashraf Rabia Hussain
author_sort	Zahra Hasan
title	CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.
title_short	CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.
title_full	CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.
title_fullStr	CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.
title_full_unstemmed	CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.
title_sort	ccl2 responses to mycobacterium tuberculosis are associated with disease severity in tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/124c03e80c094ada91d79ccb54f1e17a
work_keys_str_mv	AT zahrahasan ccl2responsestomycobacteriumtuberculosisareassociatedwithdiseaseseverityintuberculosis AT jacquelinemcliff ccl2responsestomycobacteriumtuberculosisareassociatedwithdiseaseseverityintuberculosis AT hazelmdockrell ccl2responsestomycobacteriumtuberculosisareassociatedwithdiseaseseverityintuberculosis AT bushrajamil ccl2responsestomycobacteriumtuberculosisareassociatedwithdiseaseseverityintuberculosis AT muhammadirfan ccl2responsestomycobacteriumtuberculosisareassociatedwithdiseaseseverityintuberculosis AT mussaratashraf ccl2responsestomycobacteriumtuberculosisareassociatedwithdiseaseseverityintuberculosis AT rabiahussain ccl2responsestomycobacteriumtuberculosisareassociatedwithdiseaseseverityintuberculosis
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CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.

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