Vaccination of mice with salmonella expressing VapA: mucosal and systemic Th1 responses provide protection against Rhodococcus equi infection.
Conventional vaccines to prevent the pneumonia caused by Rhodococcus equi have not been successful. We have recently demonstrated that immunization with Salmonella enterica Typhimurium expressing the VapA antigen protects mice against R. equi infection. We now report that oral vaccination of mice with this recombinant strain results in high and persistent fecal levels of antigen-specific IgA, and specific proliferation of the spleen cells of immunized mice in response to the in vitro stimulation with R. equi antigen. After in vitro stimulation, spleen cells of immunized mice produce high levels of Th1 cytokines and show a prominent mRNA expression of the Th1 transcription factor T-bet, in detriment of the Th2 transcription factor GATA-3. Following R. equi challenge, a high H2O2, NO, IL-12, and IFN-gamma content is detected in the organs of immunized mice. On the other hand, TNF-alpha and IL-4 levels are markedly lower in the organs of vaccinated mice, compared with the non-vaccinated ones. The IL-10 content and the mRNA transcription level of TGF-beta are also higher in the organs of immunized mice. A greater incidence of CD4+ and CD8+ T cells and B lymphocytes is verified in vaccinated mice. However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4+CD25+Foxp3+ T cells. Finally, we show that the vaccination confers a long-term protection against R. equi infection. Altogether, these data indicate that the oral vaccination of mice with S. enterica Typhimurium expressing VapA induces specific and long-lasting humoral and cellular responses against the pathogen, which are appropriately regulated and allow tissue integrity after challenge.
Oliveira
Aline F
AF
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Ruas
Luciana P
LP
Cardoso
Silvia A
SA
Soares
Sandro G
SG
Roque-Barreira
Maria-Cristina
MC
D000193:Actinomycetales Infections / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D001483:Base Sequence; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016929:Rhodococcus equi / Q000276:immunology*; D019779:Salmonella enterica / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D000098815:T-bet Transcription Factor
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D017931:DNA Primers; D050990:GATA3 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D009569:Nitric Oxide; D006861:Hydrogen Peroxide