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Infection and Immunity, May 2008, p. 2008-2017, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.01691-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

T Cells Help To Amplify Inflammatory Responses Induced by Salmonella enterica Serotype Typhimurium in the Intestinal Mucosa{triangledown}

Ivan Godinez, Takeshi Haneda, Manuela Raffatellu, Michael D. George, Tatiane A. Paixão, Hortensia G. Rolán, Renato L. Santos, Satya Dandekar, Renée M. Tsolis, and Andreas J. Bäumler*

Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, California

Received 18 December 2007/ Returned for modification 18 February 2008/ Accepted 6 March 2008

Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the ceca of streptomycin-pretreated mice. We determined global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. The gene expression profile was dominated by T-cell-derived cytokines and genes whose expression is known to be induced by these cytokines. Markedly increased mRNA levels of genes encoding gamma interferon (IFN-{gamma}), interleukin-22 (IL-22), and IL-17 were detected by quantitative real-time PCR. Furthermore, the mRNA levels of genes whose expression is induced by IFN-{gamma}, IL-22, or IL-17, including genes encoding macrophage inflammatory protein 2 (MIP-2), inducible nitric oxide synthase (Nos2), lipocalin-2 (Lcn2), MIP-1{alpha}, MIP-1β, and keratinocyte-derived cytokine (KC), were also markedly increased. To assess the importance of T cells in orchestrating this proinflammatory gene expression profile, we depleted T cells by using a monoclonal antibody prior to investigating cecal inflammation caused by serotype Typhimurium in streptomycin-pretreated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in gross pathology, a significantly reduced recruitment of neutrophils, and a marked reduction in mRNA levels of Ifn-{gamma}, Il-22, Il-17, Nos2, Lcn2, and Kc. Our results suggest that T cells play an important role in amplifying inflammatory responses induced by serotype Typhimurium in the cecal mucosa.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA 95616-8645. Phone: (530) 754-7225. Fax: (530) 754-7240. E-mail: ajbaumler{at}ucdavis.edu

{triangledown} Published ahead of print on 17 March 2008.

Editor: A. Camilli

Infection and Immunity, May 2008, p. 2008-2017, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.01691-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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