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Infection and Immunity, June 2003, p. 3337-3342, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3337-3342.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Differential Induction of Interleukin-10 and Interleukin-12 in Dendritic Cells by Microbial Toll-Like Receptor Activators and Skewing of T-Cell Cytokine Profiles

Hai Qi,1 Timothy L. Denning,2,{dagger} and Lynn Soong1,2*

Department of Pathology,1 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-10702

Received 8 November 2002/ Returned for modification 24 January 2003/ Accepted 6 March 2003

Dendritic cells (DCs) discriminate different microbial pathogens and induce T-cell responses of appropriate effector phenotypes accordingly. Microbial recognition and differentiation are mediated in part by pattern recognition receptors such as Toll-like receptors (TLRs), whereas the development of T-cell effector functions is critically dependent on DC-derived cytokines such as interleukin-12 (IL-12) and IL-10. However, it is not entirely clear to what extent various microbial TLR activators could induce different functional states of DCs that favor different T-cell effector phenotypes. Toward a better understanding of this issue, we examined IL-10 and IL-12 production and T-cell-polarizing potentials of murine bone marrow-derived DCs after stimulation by three microbial TLR activators, namely, lipopolysaccharide (LPS), peptidoglycan (PGN), and zymosan. We found that the three stimuli induced drastically different profiles of IL-10 and IL-12 production in DCs. Further, these stimuli differentially conditioned CD40-dependent IL-10 and IL-12 production by DCs. Finally, LPS-, PGN-, and zymosan-stimulated DCs primed distinct T-cell cytokine profiles. Our results support the notion that microbe-specific information sensed through different TLRs by DCs is linked to differential Th priming through DC-derived cytokines.

* Corresponding author. Mailing address: 301 University Blvd., Medical Research Bldg. 3.132, Galveston, TX 77555-1070. Phone: (409) 772-8149. Fax: (409) 747-6869. E-mail: lysoong{at}utmb.edu.

Editor: W. A. Petri, Jr.

{dagger} Present address: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121.

Infection and Immunity, June 2003, p. 3337-3342, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3337-3342.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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