Abstract:
:Tuberculous pleurisy allows the study of human cells at the site of active Mycobacterium tuberculosis infection. In this study, we found that among pleural fluid (PF) lymphocytes, natural killer (NK) cells are a major source of early gamma interferon (IFN-gamma) upon M. tuberculosis stimulation, leading us to investigate the mechanisms and molecules involved in this process. We show that the whole bacterium is the best inducer of IFN-gamma, although a high-molecular-weight fraction of culture filtrate proteins from M. tuberculosis H37Rv and the whole-cell lysate also induce its expression. The mannose receptor seems to mediate the inhibitory effect of mannosylated lipoarabinomannan, and Toll-like receptor 2 and 4 agonists activate NK cells but do not induce IFN-gamma like M. tuberculosis does. Antigen-presenting cells (APC) and NK cells bind M. tuberculosis, and although interleukin-12 is required, it is not sufficient to induce IFN-gamma expression, indicating that NK cell-APC contact takes place. Indeed, major histocompatibility complex class I, adhesion, and costimulatory molecules as well as NK receptors regulate IFN-gamma induction. The signaling pathway is partially inhibited by dexamethasone and sensitive to Ca2+ flux and cyclosporine. Inhibition of p38 and extracellular-regulated kinase mitogen-activated protein kinase pathways reduces the number of IFN-gamma+ NK cells. Phosphorylated p38 (p-p38) is detected in ex vivo PF-NK cells, and M. tuberculosis triggers p-p38 in PF-NK cells at the same time that binding between NK and M. tuberculosis reaches its maximum value. Thus, interplay between M. tuberculosis and NK cells/APC triggering IFN-gamma would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a type 1 profile.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Schierloh P,Yokobori N,Alemán M,Landoni V,Geffner L,Musella RM,Castagnino J,Baldini M,Abbate E,de la Barrera SS,Sasiain MCdoi
10.1128/IAI.00381-07subject
Has Abstractpub_date
2007-11-01 00:00:00pages
5325-37issue
11eissn
0019-9567issn
1098-5522pii
IAI.00381-07journal_volume
75pub_type
杂志文章abstract::Depressed Th1 responses are a prominent feature of human tuberculosis, but an enhanced Th2 response has not been detected in peripheral blood T cells stimulated in vitro with Mycobacterium tuberculosis. In disease due to Mycobacterium leprae, Th2 cells predominate in tissue lesions of patients with extensive disease b...
journal_title:Infection and immunity
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doi:10.1128/IAI.64.4.1351-1356.1996
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abstract::Cholera enterotoxin and the related heat-labile enterotoxins of Escherichia coli enter their target cells through noncoated vesicles, but how the toxins are processed intracellularly and how they get to their targeted enzyme, adenylate cyclase, remain to be defined. Brefeldin A, an inhibitor of the trans-Golgi network...
journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.57.12.3751-3756.1989
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.64.10.4067-4073.1996
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.3.1055-1061.1993
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.12.4.841-850.1975
更新日期:1975-10-01 00:00:00
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journal_title:Infection and immunity
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