| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 21, 18753-18762, May 24, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Microbiology and Immunology and
Biotechnology Laboratory, University of British Columbia,
Vancouver, British Columbia V6T 1Z3, Canada
Host responses during the later stages of
Salmonella-macrophage interactions are critical to
controlling infection but have not been well characterized. After
24 h of infection, nearly half of interferon-
Macrophages Inhibit Salmonella Typhimurium
Replication through MEK/ERK Kinase and Phagocyte NADPH Oxidase
Activities*
and
-primed murine RAW
264.7 macrophage-like cells infected by Salmonella enterica
serovar Typhimurium contained filamentous bacteria. Bacterial
filamentation indicates a defect in completing replication and has been
previously observed in bacteria responding to a variety of stresses. To
understand whether macrophage gene expression was responsible for this
effect on Salmonella Typhimurium replication, we
used gene arrays to profile interferon--primed RAW 264.7 cell gene
expression following infection. We observed an increase in MEK1 kinase
mRNA at 8 h, an increase in MEK protein at 24 h, and
measured phosphorylation of MEK's downstream target kinase, ERK1/2,
throughout the 24-h infection period. Treatment of cells with MEK
kinase inhibitors significantly reduced numbers of filamentous bacteria
observed within macrophages after 24 h and increased the number of
intracellular colony-forming units. Phagocyte NADPH oxidase
inhibitors and antioxidants also significantly reduced bacterial
filamentation. Either MEK kinase or phagocyte oxidase inhibitors could
be added 4-8 h after infection and still significantly decrease
bacterial filamentation. Oxidase activity appears to mediate bacterial
filamentation in parallel to MEK kinase signaling, while inducible
nitric-oxide synthase inhibitors had no significant effect on
bacterial morphology. In summary, Salmonella Typhimurium
infection of interferon--primed macrophages triggers a MEK kinase
cascade at later infection times, and both MEK kinase and phagocyte
NADPH oxidase activity impair bacterial replication. These two
signaling pathways mediate a host bacteriostatic pathway and may play
an important role in innate host defense against intracellular pathogens.
*
This work was supported by operating grants from the
Canadian Bacterial Diseases Network and the Canadian Institutes for
Health Research (CIHR).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by studentships from the Natural Sciences and
Engineering Research Council, CIHR, and the Michael Smith Foundation for Health Research.
§
Recipient of a CIHR Distinguished Investigator Award and is a
Howard Hughes International Research Scholar. To whom correspondence should be addressed: Biotechnology Laboratory, University of
British Columbia, Rm. 237 Wesbrook Bldg., 6174 University
Blvd., Vancouver, British Columbia V6T 1Z3, Canada. Tel.:
604-822-2210; Fax: 604-822-9830; E-mail:
bfinlay@interchange.ubc.ca.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. M. Eswarappa, K. K. Panguluri, M. Hensel, and D. Chakravortty The yejABEF operon of Salmonella confers resistance to antimicrobial peptides and contributes to its virulence Microbiology, February 1, 2008; 154(2): 666 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Shi, J. N. Adkins, J. R. Coleman, A. A. Schepmoes, A. Dohnkova, H. M. Mottaz, A. D. Norbeck, S. O. Purvine, N. P. Manes, H. S. Smallwood, et al. Proteomic Analysis of Salmonella enterica Serovar Typhimurium Isolated from RAW 264.7 Macrophages: IDENTIFICATION OF A NOVEL PROTEIN THAT CONTRIBUTES TO THE REPLICATION OF SEROVAR TYPHIMURIUM INSIDE MACROPHAGES J. Biol. Chem., September 29, 2006; 281(39): 29131 - 29140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Suvarnapunya and M. A. Stein DNA base excision repair potentiates the protective effect of Salmonella Pathogenicity Island 2 within macrophages Microbiology, February 1, 2005; 151(2): 557 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Kujat Choy, E. C. Boyle, O. Gal-Mor, D. L. Goode, Y. Valdez, B. A. Vallance, and B. B. Finlay SseK1 and SseK2 Are Novel Translocated Proteins of Salmonella enterica Serovar Typhimurium Infect. Immun., September 1, 2004; 72(9): 5115 - 5125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Rosenberger, R. L. Gallo, and B. B. Finlay Interplay between antibacterial effectors: A macrophage antimicrobial peptide impairs intracellular Salmonella replication PNAS, February 24, 2004; 101(8): 2422 - 2427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Cano, M. G. Pucciarelli, M. Martinez-Moya, J. Casadesus, and F. Garcia-del Portillo Selection of Small-Colony Variants of Salmonella enterica Serovar Typhimurium in Nonphagocytic Eucaryotic Cells Infect. Immun., July 1, 2003; 71(7): 3690 - 3698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. J. Royle, S. Totemeyer, L. C. Alldridge, D. J. Maskell, and C. E. Bryant Stimulation of Toll-Like Receptor 4 by Lipopolysaccharide During Cellular Invasion by Live Salmonella typhimurium Is a Critical But Not Exclusive Event Leading to Macrophage Responses J. Immunol., June 1, 2003; 170(11): 5445 - 5454. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
