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Infection and Immunity, January 2009, p. 76-84, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00963-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role for the Chlamydial Type III Secretion Apparatus in Host Cytokine Expression {triangledown}

Daniel Prantner1 and Uma M. Nagarajan1,2*

Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205,1 Division of Pediatric Infectious Diseases, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 722022

Received 31 July 2008/ Returned for modification 31 August 2008/ Accepted 8 October 2008

In many important human pathogens, such as Shigella and Salmonella spp., the bacterial type III secretion (T3S) apparatus is required to initiate inflammation via activation of caspase-1- or NF-{kappa}B-dependent genes. Using an ex vivo infection model, the goal of the present study was to determine whether the chlamydial T3S apparatus also modulates the host inflammatory response. Infections of mouse peritoneal macrophages were performed with Chlamydia muridarum, and the expression of inflammatory cytokines was monitored by quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. Since there is no current genetic system for Chlamydia spp., blockade of T3S was accomplished pharmacologically using a T3S inhibitor called INP0007. It has been previously shown that INP0007 also blocks chlamydial growth in vitro and that the addition of exogenous iron completely reverses this deficit. The addition of iron to INP0007-treated C. muridarum-infected macrophages not only restored chlamydial growth deficit caused by INP0007 but also led to a multi-inclusion phenotype. Overall, T3S inhibition led to decreased interleukin-6 (IL-6), IL-1β, and CXCL10, whereas the tumor necrosis factor alpha levels were unchanged. Rescue of chlamydial growth by addition of iron sulfate did not restore cytokine production, implying that the decreased expression of many cytokines during infection was dependent on T3S and not solely on growth. In addition, the observation that the greatest effects of INP0007 were seen at late time points during infection suggests that a temporally regulated T3S effector protein(s) may be triggering the host cytokine response.

* Corresponding author. Mailing address: Division of Pediatric Infectious Diseases, Arkansas Children's Hospital Research Institute, 1120 Marshall Street, Rm. 2052, Little Rock, AR 72202. Phone: (501) 364-2479. Fax: (501) 364-2403. E-mail: nagarajanuma{at}uams.edu

{triangledown} Published ahead of print on 13 October 2008.

Editor: A. J. Bäumler

Infection and Immunity, January 2009, p. 76-84, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00963-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Prantner, D., Darville, T., Sikes, J. D., Andrews, C. W. Jr., Brade, H., Rank, R. G., Nagarajan, U. M. (2009). Critical Role for Interleukin-1{beta} (IL-1{beta}) during Chlamydia muridarum Genital Infection and Bacterial Replication-Independent Secretion of IL-1{beta} in Mouse Macrophages. Infect. Immun. 77: 5334-5346 [Abstract] [Full Text]  


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