In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 1 ( 2006-01-03), p. 141-146
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-1β, 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-1β mRNA synthesis and intracellular pro-IL-1β production, only live Francisella induced enhanced IL-1β 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-1β 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-1β processing and release that was induced by Francisella . Blocking bacterial escape from the phagosome into the cytosol also decreased IL-1β but not IL-8 release. These findings demonstrate that Francisella organisms efficiently induce IL-1β processing and release in fresh monocytes by means of a sensing system that requires the uptake of live bacteria capable of phagosome escape.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0504271103
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2006
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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