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Infection and Immunity, July 2001, p. 4521-4527, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4521-4527.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Protection against Pulmonary Infection with Pseudomonas aeruginosa following Immunization with P. aeruginosa-Pulsed Dendritic Cells

Stefan Worgall,1,2,* Toshiaki Kikuchi,1 Ravi Singh,3 Katherine Martushova,1 Leah Lande,1 and Ronald G. Crystal1,3,4

Division of Pulmonary and Critical Care Medicine,1 Department of Pediatrics,2 Belfer Gene Therapy Core Facility,3 and Institute of Genetic Medicine,4 Weill Medical College of Cornell University, New York, New York

Received 8 December 2000/Returned for modification 9 February 2001/Accepted 9 April 2001

To develop a Pseudomonas aeruginosa vaccine that allows the host immune system to select the antigens, we hypothesized that dendritic cells (DC) pulsed with P. aeruginosa would induce protective immunity against pulmonary infections with P. aeruginosa. Incubation of murine bone marrow-derived DC with P. aeruginosa in vitro led to uptake of P. aeruginosa and activation of the DC. Spleen-derived CD4+ cells from mice immunized with P. aeruginosa-pulsed DC showed increased proliferation, demonstrating that DC pulsed with P. aeruginosa were capable of eliciting a P. aeruginosa-specific immune response. To evaluate if P. aeruginosa-pulsed DC can induce protective immunity against P. aeruginosa pulmonary infection, DC incubated with P. aeruginosa in vitro were administered systemically to syngeneic mice, and the mice were then challenged by intrapulmonary infection with P. aeruginosa (5 × 104 CFU/mouse) 13 days later. Unimmunized control mice and mice who had previously received naive DC or DC stimulated with lipopolysaccharide or Escherichia coli died within 72 h. In contrast, 45% of mice receiving P. aeruginosa-pulsed DC demonstrated prolonged survival (>14 days). Finally, DC-pulsed with heat-inactivated P. aeruginosa protected CD8-/- but not CD4-/- mice, demonstrating that CD4+ T cells were required for the DC pulsed with P. aeruginosa to induce protective immunity.

* Corresponding author. Mailing address: Weill Medical College of Cornell University, New York Presbyterian Hospital, 520 East 70th St., ST 505, New York, NY 10021. Phone: (212) 746-2258. Fax: (212) 746-8383. E-mail: geneticmedicine{at}med.cornell.edu.

Infection and Immunity, July 2001, p. 4521-4527, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4521-4527.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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