Mycobacterium tuberculosis 6-kDa Early Secreted Antigenic Target ESAT-6 protein downregulates Lipopolysaccharide induced c-myc expression by modulating the Extracellular Signal Regulated Kinases 1-2Reportar como inadecuado




Mycobacterium tuberculosis 6-kDa Early Secreted Antigenic Target ESAT-6 protein downregulates Lipopolysaccharide induced c-myc expression by modulating the Extracellular Signal Regulated Kinases 1-2 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Immunology

, 8:24

First Online: 03 October 2007Received: 28 May 2007Accepted: 03 October 2007

Abstract

BackgroundMycobacterium tuberculosis Mtb causes death of 2–3 million people every year. The persistence of the pathogenic mycobacteria inside the macrophage occurs through modulation of host cell signaling which allows them, unlike the other non-pathogenic species, to survive inside the host. The secretory proteins of M. tuberculosis have gained attention in recent years both as vaccine candidates and diagnostic tools; they target the immune system and trigger a putatively protective response; however, they may also be involved in the clinical symptoms of the disease.

ResultsOur studies showed that RD-1-encoded secretory protein ESAT-6 is involved in modulation of the mitogen-activated protein MAP kinase-signaling pathway inside the macrophage. ESAT-6 induced phosphorylation of extracellular signal-regulated kinases 1-2 ERK1-2 in the cytoplasm but not in the nucleus, which normally is the case for MAP kinases. ESAT-6 also antagonized LPS-induced ERK1-2 phosphorylation in the nucleus. Stimulation of cells by ESAT-6 along with sodium orthovanadate a tyrosine phosphatase inhibitor restored phosphorylation of ERK1-2 in the nucleus, suggesting active dephosphorylation of ERK1-2 by some putative phosphatases in the nucleus. Further, ESAT-6 was found to down regulate the expression of LPS-inducible gene c-myc in an ERK1-2-dependent manner.

ConclusionThis study showed the effect of secretory proteins of M. tuberculosis in the modulation of macrophage signaling pathways particularly ERK1-2 MAP kinase pathway. This modulation appears to be achieved by limiting the ERK1-2 activation in the nucleus which ultimately affects the macrophage gene expression. This could be a mechanism by which secretory proteins of Mtb might modulate gene expression inside the macrophages.

AbbreviationsATCC – American Type Culture CollectionERK1-2 – Extracellular Signal Regulated Kinases1-2, ESAT-6 – Early Secreted Antigenic Target 6-kDa, LPS – Lipopolysaccharide, MBP – Myelin Basic Protein, Mtb –Mycobacterium tuberculosis, MAP kinase – Mitogen Activated Protein kinase, pERK1-2 – phosphoERK1-2, p-NPP –para-nitrophenyl phosphate.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2172-8-24 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Niladri Ganguly - Pham H Giang - Sandip K Basu - Fayaz Ahmad Mir - Imran Siddiqui - Pawan Sharma

Fuente: https://link.springer.com/



DESCARGAR PDF




Documentos relacionados