| Mast cell/IL-4 control of Francisella tularensis replication and host cell death is associated with increased ATP production and phagosomal acidification. | |
| | |
MedLine Citation:
|
PMID: 20861832 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Mast cells are now recognized as effective modulators of innate immunity. We recently reported that mast cells and secreted interleukin-4 (IL-4) effectively control intramacrophage replication of Francisella tularensis Live Vaccine Strain (LVS), and that mice deficient in mast cells or IL-4 receptor (IL-4R(-/-)) exhibit greater susceptibility to pulmonary challenge. In this study, we further evaluated the mechanism(s) by which mast cells/IL-4 control intramacrophage bacterial replication and host cell death, and found that IL-4R(-/-) mice exhibited significantly greater induction of active caspase-3 within lung macrophages than wild-type animals following intranasal challenge with either LVS or the human virulent type A strain SCHU S4. Treatment of LVS-infected bone-marrow-derived macrophages with a pancaspase inhibitor (zVAD) did not alter bacterial replication, but minimized active caspase-3 and other markers (Annexin V and propidium iodide) of cell death, whereas treatment with both rIL-4 and zVAD resulted in concomitant reduction of both parameters, suggesting that inhibition of bacterial replication by IL-4 was independent of caspase activation. Interestingly, IL-4-treated infected macrophages exhibited significantly increased ATP production and phagolysosomal acidification, as well as enhanced mannose receptor upregulation and increased internalization with acidification, which correlated with observations in mast cell-macrophage co-cultures, with resultant decreases in F. tularensis replication. |
| | |
Authors:
|
A R Rodriguez; J-J Yu; A K Murthy; M N Guentzel; K E Klose; T G Forsthuber; J P Chambers; M T Berton; B P Arulanandam |
Publication Detail:
|
Type: Journal Article Date: 2010-09-22 |
Journal Detail:
|
Title: Mucosal immunology Volume: 4 ISSN: 1935-3456 ISO Abbreviation: Mucosal Immunol Publication Date: 2011 Mar |
Date Detail:
|
Created Date: 2011-02-15 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101299742 Medline TA: Mucosal Immunol Country: United States |
Other Details:
|
Languages: eng Pagination: 217-26 Citation Subset: IM |
Affiliation:
|
Department of Biology, South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, Texas, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Glutamatergic model psychoses: prediction error, learning, and inference.
Next Document: Topical immunization strategies.