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Infection and Immunity, April 2008, p. 1558-1564, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01331-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification and Characterization of Chlamydia pneumoniae-Specific Proteins That Activate Tumor Necrosis Factor Alpha Production in RAW 264.7 Murine Macrophages{triangledown}

Shinn-Jong Jiang, Cho-Chou Kuo, Mark W. Berry, Amy W. Lee, and Lee Ann Campbell*

Departments of Pathobiology and Epidemiology, University of Washington, Box 357328, Seattle, Washington 98195-3873

Received 3 October 2007/ Returned for modification 22 October 2007/ Accepted 22 January 2008

Chlamydia pneumoniae is a common respiratory pathogen, which activates macrophages to induce inflammatory cytokines that may promote atherosclerosis. However, the antigens that induce macrophage activation have not been well defined. In the current study, three chlamydial proteins which are recognized during human infection, outer membrane protein 2 (OMP2) and two 53-kDa proteins (Cpn 0980 and Cpn 0809), were investigated to determine whether they activate macrophages and, if they do, what mechanism they use for this activation. It was shown that these three proteins could (i) induce expression of tumor necrosis factor alpha (TNF-{alpha}) and tissue factor and (ii) induce phosphorylation of p44/42 mitogen-activated protein kinases (MAPK) and activation of early growth response factor 1 (Egr-1). Control proteins, the N-terminal fragment of polymorphic membrane protein 8 and the thioredoxin portion of the fusion protein, had no effect on macrophages. Treatment of cells with a MEK1/2 inhibitor, U0126, dramatically reduced the phosphorylation of ERK, activation of Egr-1, and expression of TNF-{alpha} in macrophages treated with recombinant proteins. Toll-like receptors (TLRs) act as sensors for microbial antigens and can signal via the MAPK pathway. Chlamydial protein-induced expression of TNF-{alpha} was significantly reduced in macrophages lacking TLR2 or TLR4. These findings suggest that C. pneumoniae may activate macrophages through OMP2, Cpn 0980, and Cpn 0809 in addition to cHSP60 and that activation occurs via TLR2 or TLR4, Egr-1, and MAPK pathways.

* Corresponding author. Mailing address: Departments of Pathobiology and Epidemiology, University of Washington, Box 357328, Seattle, WA 98195-3873. Phone: (206) 543-8689. Fax: (206) 543-3873. E-mail: lacamp{at}u.washington.edu

{triangledown} Published ahead of print on 28 January 2008.

Editor: R. P. Morrison

Infection and Immunity, April 2008, p. 1558-1564, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01331-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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