This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kikuchi, T. Articles by Nukiwa, T. Search for Related Content PubMed PubMed Citation Articles by Kikuchi, T. Articles by Nukiwa, T.

 Previous Article  |  Next Article 

Infection and Immunity, September 2005, p. 5350-5357, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5350-5357.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila

Toshiaki Kikuchi,^1* Sita Andarini,¹ Hong Xin,¹ Kazunori Gomi,¹ Yutaka Tokue,¹ Yasuo Saijo,¹ Tasuku Honjo,² Akira Watanabe,¹ and Toshihiro Nukiwa¹

Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan,¹ Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan²

Received 11 January 2005/ Returned for modification 24 February 2005/ Accepted 13 April 2005

Legionnaires' disease is clinically manifested as severe pneumonia caused by Legionella pneumophila. However, the dendritic cell (DC)-centered immunological framework of the host defense against L. pneumophila has not been fully delineated. For this study, we focused on a potent chemoattractant for lymphocytes, fractalkine/CX3CL1, and observed that the fractalkine expression of DCs was somewhat up-regulated when they encountered L. pneumophila. We therefore hypothesized that fractalkine expressed by Legionella-capturing DCs is involved in the induction of T-cell-mediated immune responses against Legionella, which would be enhanced by a genetic modulation of DCs to overexpress fractalkine. In vivo immunization-challenge experiments demonstrated that DCs modified with a recombinant adenovirus vector to overexpress fractalkine (AdFKN) and pulsed with heat-killed Legionella protected immunized mice from a lethal Legionella infection and that the generation of in vivo protective immunity depended on the host lymphocyte subsets, including CD4⁺ T cells, CD8⁺ T cells, and B cells. Consistent with this, immunization with AdFKN/Legionella/DC induced significantly higher levels of serum anti-Legionella antibodies of several isotypes than those induced by control immunizations. Further analysis of spleen cells from the immunized mice indicated that the AdFKN/Legionella/DC immunization elicited Th1-dominated immune responses to L. pneumophila. These observations suggest that fractalkine may play an important role in the DC-mediated host defense against intracellular pathogens such as L. pneumophila.

---

* Corresponding author. Mailing address: Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aobaku, Sendai 980-8575, Japan. Phone: (81)22-717-8539. Fax: (81)22-717-8549. E-mail: kikuchi{at}idac.tohoku.ac.jp.

Editor: J. N. Weiser

---

Infection and Immunity, September 2005, p. 5350-5357, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5350-5357.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Karaolis, D. K. R., Newstead, M. W., Zeng, X., Hyodo, M., Hayakawa, Y., Bhan, U., Liang, H., Standiford, T. J. (2007). Cyclic Di-GMP Stimulates Protective Innate Immunity in Bacterial Pneumonia. Infect. Immun. 75: 4942-4950 [Abstract] [Full Text]