ABSTRACT
BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) is pathogenic to humans, by causing pulmonary inflammation or bronchitis in both adolescents and young adults. However, the molecular signals linking C. pneumoniae components to inflammation remain elusive. This study was to investigate the effect of Chlamydia-specific Cpn0423 of C. pneumoniae on C. pneumoniae-mediated inflammation. RESULTS: Cpn0423 was detected outside of C. pneumoniae inclusions, which induced production of several cytokines including macrophage inflammatory protein-2 (MIP-2) and interleukins (ILs). Production of the Cpn0423-induced cytokines was markedly reduced in cells pretreated with NOD2-siRNA, but not with negative control oligonucleotides. Mice treated with Cpn0423 through intranasal administration exhibited pulmonary inflammation as evidenced by infiltration of inflammatory cells, increased inflammatory scores in the lung histology, recruitment of neutrophils and increased cytokines levels in the BALF. CONCLUSION: Cpn0423 could be sensed by NOD2, which was identified as an essential element in a pathway contributing to the development of C. pneumoniae -mediated inflammation.
Subject(s)
Bacterial Proteins/immunology , Chlamydophila Infections/immunology , Chlamydophila pneumoniae/immunology , Inflammation Mediators/immunology , Nod2 Signaling Adaptor Protein/immunology , Pneumonia, Bacterial/microbiology , Animals , Bacterial Proteins/genetics , Chemokine CXCL2/genetics , Chemokine CXCL2/immunology , Chlamydophila Infections/genetics , Chlamydophila Infections/microbiology , Chlamydophila pneumoniae/genetics , Humans , Interleukins/genetics , Interleukins/immunology , Lung/immunology , Male , Mice , Mice, Inbred C57BL , Nod2 Signaling Adaptor Protein/genetics , Pneumonia, Bacterial/genetics , Pneumonia, Bacterial/immunologyABSTRACT
Chlamydia psittaci is an obligate intracellular bacteria that causes respiratory disease in poultry and humans. Currently, there are no licensed vaccines against chlamydial infection in humans. The transmembrane head protein CPSIT_0846 of C. psittaci is a putative member of the larger Inc protein family. In this study, we investigated immunogenicity and protective efficacy of the recombinant CPSIT_0846 protein in BALB/c mice. Mice immunized with CPSIT_0846 developed strong T-lymphocyte responses that were recalled by the immunogen CPSIT_0846 in an in vitro restimulation assay. These T cells displayed a strong Th1-biased cytokine profile with high levels of IFN-γ. At the same time, a strong humoral immune response was also detected in the immunized mice with high titers of Chlamydia psittaci-specific serum IgG antibodies. More importantly, the robust immune responses correlated well with significantly reduced chlamydial burden and inflammatory pathology in the mouse lungs upon an airway challenge infection. The above results together suggest that the CPSIT_0846 protein may be a potential vaccine candidate antigen for inducing protection against C. psittaci infection and disease in the airway.
Subject(s)
Bacterial Proteins/immunology , Chlamydophila psittaci/immunology , Psittacosis/immunology , Recombinant Proteins/immunology , Animals , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Bacterial Proteins/administration & dosage , Bacterial Proteins/genetics , Cytokines/metabolism , Disease Models, Animal , Female , HeLa Cells , Humans , Immunization , Lung/immunology , Lung/microbiology , Lung/pathology , Mice , Mice, Inbred BALB C , Psittacosis/metabolism , Psittacosis/microbiology , Psittacosis/prevention & control , Recombinant Proteins/administration & dosage , Recombinant Proteins/genetics , Th1 Cells/immunology , Th1 Cells/metabolismABSTRACT
Chlamydia psittaci is a zoonotic pathogen with a broad host range that can lead to severe respiratory and systemic disease in humans. Currently, an effective commercial vaccine against C. psittaci infection is not available. The chlamydial plasmid is an important virulence factor and encodes plasmid proteins that play important roles in chlamydial infection and the corresponding immune response. In this study, we assessed the efficacy of vaccination with plasmid proteins at preventing C. psittaci lung infection in a murine model. BALB/c mice were immunized intraperitoneally, three times at 2-week intervals, with purified recombinant CPSIT_p8 protein and then infected with C. psittaci. Immunization significantly decreased chlamydial load in the lungs of infected mice, resulted in a lower level of IFN-γ, and reduced the extent of inflammation. In vivo or in vitro neutralization of C. psittaci with sera collected from immunized mice did not reduce the amount of viable C. psittaci in the lungs of mice, indicating that CPSIT_p8-specific antibodies do not have neutralizing capacity. Furthermore, confocal fluorescence microscopy using a mouse anti-CPSIT_p8 antibody revealed that CPSIT_p8 was localized inside the inclusion of C. psittaci 6BC-infected cells. Our results demonstrate that CPSIT_p8 protein induces significant protective immunity against challenge with C. psittaci in mice and represents a promising new vaccine candidate for the prevention of C. psittaci infection.
