当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release.

Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release.

Abstract：

:Macrophage responses to Francisella infection have been characterized previously by subdued proinflammatory responses; however, these studies have generally focused on macrophage cell lines or monocyte-derived macrophages. Therefore, we studied the ability of fresh human blood monocytes to engulf and respond to Francisella by using the live vaccine strain variant and Francisella novicida. Because Francisella organisms have been reported to escape from the phagolysosome into the cytosol, we hypothesized that this escape may trigger the activation of caspase-1. Francisella tularensis variants were readily taken up by fresh human CD14(+) monocytes, inducing the release of IL-1beta, as well as IL-8, in a time- and dose-dependent fashion. Importantly, whereas live and dead Escherichia coli, F. novicida, and live vaccine strain, as well as the LPS of E. coli, were able to induce abundant IL-1beta mRNA synthesis and intracellular pro-IL-1beta production, only live Francisella induced enhanced IL-1beta processing and release (51 +/- 10 vs. 7.1 +/- 2.1 ng/ml, for F. novicida vs. E. coli LPS; P = 0.0032). Cytochalasin D blocked the Francisella internalization and the Francisella-induced monocyte IL-1beta processing and release but not that induced by the exogenous stimulus E. coli LPS. Also, killing bacteria did not block uptake but significantly diminished the IL-1beta processing and release that was induced by Francisella. Blocking bacterial escape from the phagosome into the cytosol also decreased IL-1beta but not IL-8 release. These findings demonstrate that Francisella organisms efficiently induce IL-1beta processing and release in fresh monocytes by means of a sensing system that requires the uptake of live bacteria capable of phagosome escape.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Gavrilin MA,Bouakl IJ,Knatz NL,Duncan MD,Hall MW,Gunn JS,Wewers MD

doi

10.1073/pnas.0504271103

keywords:

subject

Has Abstract

pub_date

2006-01-03 00:00:00

pages

141-6

issue

1

eissn

0027-8424

issn

1091-6490

pii

0504271103

journal_volume

103

pub_type

杂志文章

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