Abstract
Legionella pneumophila, an intracellular bacterium, may cause life-threatening pneumonia in immunocompromised individuals. Mononuclear cells and antibodies have been reported to be associated with the host defense response against L. pneumophila. This study is to determine whether Legionella peptidoglycan-associated lipoprotein (PAL)-specific CD8+ T cells are directly associated with protection against L. pneumophila, with a focus on potential epitopes. Synthetic peptides derived from PAL of L. pneumophila were obtained and tested through in vitro and in vivo cytotoxic T lymphocyte (CTL) assays for immunogenicity. PAL DNA vaccines or a peptide epitope with or without CpG-oligodeoxynucleotides (ODN) was evaluated for protection against L. pneumophila infection in animal models. When mice were immunized with DNA vaccines expressing the PAL of L. pneumophila, they were significantly protected against a lethal challenge with L. pneumophila through induction of antigen-specific CD8+ CTLs. Of the 13 PAL peptides tested, PAL92-100 (EYLKTHPGA) was the most immunogenic and induced the strongest CTL responses. When mice were immunized with the PAL92-100 peptide plus CpG-ODN, they were protected against the lethal challenge, while control mice died within 3–6 days after the challenge. Consistent with lung tissue histological data, bacterial counts in the lungs of immunized mice were significantly lower than those in control mice. Also, the amino acid sequence of PAL92-100 peptides is conserved among various Legionella species. To our knowledge, this study is the first to demonstrate that PAL92-100-specific CD8+ T cells play a central role in the host defense response against L. pneumophila.
Highlights
Legionella pneumophila is the causative pathogen of a severe form of pneumonia, Legionnaires' disease, with high mortality and morbidity
We demonstrated that peptidoglycan-associated lipoprotein (PAL)-specific CD8+ cytotoxic T lymphocyte (CTL) were responsible for protection from infection with L. pneumophila
We previously reported that both PAL DNA and Recombinant PAL (rPAL) vaccines induce antigen-specific antibody and CTL responses [20]
Summary
Legionella pneumophila is the causative pathogen of a severe form of pneumonia, Legionnaires' disease, with high mortality and morbidity. L. pneumophila enters the human respiratory tract as a result of inhalation of aerosols from a contaminated water source, and thereafter infects human alveolar macrophage and lung epithelial cells [5,6,7,8]. In human studies, activated mononuclear cells inhibited the intracellular multiplication of L. pneumophila [9, 11]. Alveolar macrophages were suggested to be an effector cell acting to inhibit bacterial multiplication [11]. Immunization with L. pneumophila membranes resulted in induction of strong cellular immune responses and protective immunity against a lethal challenge with L. pneumophila [13]. The major secretory and outer membrane proteins of L. pneumophila were reported to be effective at inducing protective immunity against L. pneumophila [14, 15]
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