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

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Abstract
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 .