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Immunization with mycobacterial antigens: a role for innate immunity in antigen presentation
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Department of Immunology.
(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Abstract [en]

We have found that toll-like receptor (TLR) 2 was important in the control of mycobacterial infection in the lungs. However, it is unclear how the TLR2-mediated innate immunity contributes to the development of acquired immune responses upon immunization with mycobacterial antigens. In the present study, we addressed this issue by immunizing TLR2 knockout (TLR2-/-) and wild-type (WT) mice with mycobacterial 19kDa (TLR2 ligand) or Ag85A (non-TLR2 ligand) antigens. We compared both humoral and cellular immune responses in the two mouse strains. Interferon gamma (IFN-g) responses were measured in the culture supernatants after in vitro restimulation of spleen cells with antigen alone, antigen-pulsed bone marrow derived macrophages (BMMAg) or BCG-infected BMM (BMMBCG). We found that the magnitude of antigen-specific antibody responses in serum was comparable in the two mouse strains. With regard to the two antigens, immunization with 19kDa induces more Th1 type immune responses compared to the immunization with Ag85A. We observed differences in the response of the two strains upon restimulation with antigen alone or with BMMAg regarding 19kDa. Recall IFN-g responses to 19kDa were significantly lower in the TLR2-/- mice compared to the WT mice. Interestingly, IFN-g responses to BMMBCG were similar in both strains probably due to the fact that BCG targets other cell surface molecules. The expression of CD86 in the BMMBCG was found to be TLR2-independent whereas in the BMMAg it was TLR2-dependent.

Altogether, results from this study indicate that specific immune responses could be generated in the absence of TLR2 regardless of the characteristics of the antigens (TLR2 dependent or independent) used for immunization. We discuss the relevance of innate immunity for the induction of acquired immune responses.

URN: urn:nbn:se:su:diva-39178OAI: diva2:318978
Available from: 2010-05-12 Created: 2010-05-12 Last updated: 2010-05-31
In thesis
1. Mucosal immunity against mycobacterial infection
Open this publication in new window or tab >>Mucosal immunity against mycobacterial infection
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aimed to the identification of immune biomarkers of mycobacterial infection for better diagnosis of tuberculosis (TB) and also focused on new vaccination strategies with a particular emphasis on the immune responses in the respiratory tract using murine models.

Since the lung is the natural habitat for the M. tuberculosis, we reasoned that immune responses detected locally in the lungs would be good correlates of infection (Paper I). Likewise, immune responses induced in the respiratory tract following immunization would be more effective against mycobacterial infection. We showed that cytokines (IL-12, TNF, and IFN-γ) and cytokine receptors (sTNFR1 and sTNFR2) together with specific antibodies in the respiratory tract correlated better with the bacterial burden in the organs. In Paper II, we investigated the role of the BCG vaccination as a priming vaccine in a heterologous prime-boost immunization protocol. The results showed that the neonatal BCG vaccination primed the immune system for a relevant antigen and showed a generalized adjuvant effect. Using this immunization protocol, protective immune responses in the lungs were generated independently of the route used for the booster immunization. In Paper III, We showed that exposure to mycobacterial antigens during the gestational period led to antigen transportation from the mother to the fetus and this resulted in an early priming of the fetal immune system. Immunization with the same antigen during the postnatal life increased antigen-specific recall IFN-γ responses and protection against infection. We examined the role of innate immunity for the induction of acquired immune responses upon immunization with mycobacterial antigens using TLR2 deficient mice (Paper IV). Our data indicated that suboptimal innate immune responses in the TLR2-/- mice might compromise the induction of acquired immune responses.

Overall, the current findings suggested that a better understanding of the mucosal immunity would be useful for the improvement of diagnostic procedures and the development of efficient vaccines against TB.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2010. 93 p.
Mucosal immunity, Vaccination, Diagnosis, Mycobacterial infection
National Category
Immunology in the medical area
Research subject
urn:nbn:se:su:diva-39170 (URN)978-91-7447-081-9 (ISBN)
Public defence
2010-06-18, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: ManuscriptAvailable from: 2010-05-31 Created: 2010-05-12 Last updated: 2010-05-31Bibliographically approved

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