当前位置： SCI文献检索 > INFECTION AND IMMUNITY期刊下所有文献 > The down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilli.

The down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilli.

Abstract：

:Cathepsin G (CatG) is a serine protease found in the azurophilic granules of monocytes that is known to have antimicrobial properties, but its role in Mycobacterium tuberculosis infection is unknown. We found that M. tuberculosis infection of human THP-1 monocytic cells induced the down-regulation of CatG mRNA expression, as demonstrated by gene array analysis and reverse transcription-PCR. This was associated with a concomitant decrease in CatG protein and enzymatic activity. In contrast, the expression of lysosomal cathepsins B and D was up-regulated in infected cells. This effect was also observed when THP-1 cells were induced to differentiate into adherent macrophages by exposure to bacterial lipopolysaccharide (LPS). In agreement with this, CatG expression was null in adherent macrophages isolated from bronchoalveolar lavages and normal blood. We wanted to determine if the down-regulation of CatG would be relevant to M. tuberculosis infection. First, we found that addition of CatG to THP-1 cells prior to infection resulted in decreased bacillary viability, presumably due to extracellular killing of bacilli. However, pretreatment of cells with LPS, which decreases intracellular CatG expression, resulted in increased bacillary viability. Second, we found that CatG cationic peptides killed M. tuberculosis bacilli and were five- to sevenfold more bactericidal than full-length CatG. These observations suggest that M. tuberculosis infection of human monocytic cells results in a "cathepsin switch" with down-regulation of CatG rendering M. tuberculosis bacilli more viable. Therefore, the down-regulation of CatG in macrophages is advantageous to M. tuberculosis bacilli and possibly is an important mechanism by which M. tuberculosis is able to evade the host immune defenses.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Rivera-Marrero CA,Stewart J,Shafer WM,Roman J

doi

10.1128/IAI.72.10.5712-5721.2004

keywords:

subject

Has Abstract

pub_date

2004-10-01 00:00:00

pages

5712-21

issue

eissn

0019-9567

issn

1098-5522

pii

72/10/5712

journal_volume

pub_type

杂志文章

在线工具

The down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilli.