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Influence of maternal gestational treatment with mycobacterial antigens on postnatal immunity in an experimental murine model
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
2010 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 3, e9699- p.Article in journal (Refereed) Published
Abstract [en]

It has been proposed that the immune system could be primed as early as during the fetal life and this might have an impact on postnatal vaccination. Therefore, we addressed in murine models whether gestational treatment with mycobacterial antigens could induce better immune responses in the postnatal life. METHODS/FINDINGS: BALB/c mice were treated subcutaneously (s.c.) at the second week of gestation with antigen (Ag)85A or heparin-binding hemagglutinin (HBHA) in the absence of adjuvant. Following birth, offspring mice were immunized intranasally (i.n.) with the same antigens formulated with the adjuvant cholera toxin (CT) at week 1 and week 4. One week after the last immunization, we assessed antigen-specific recall interferon gamma (IFN-gamma) responses by in vitro restimulation of lung-derived lymphocytes. Protection against infection was assessed by challenge with high dose Mycobacterium bovis Bacille Calmette-Guérin (BCG) given i.n. We found that recall IFN-gamma responses were higher in the offspring born to the treated mother compared to the untreated-mother. More importantly, we observed that the offspring born to the treated mother controlled infection better than the offspring born to the untreated mother. Since the gestational treatment was done in absence of adjuvant, essentially there was no antibody production observed in the pregnant mice and therefore no influence of maternal antibodies was expected. We hypothesized that the effect of maternal treatment with antigen on the offspring occurred due to antigen transportation through placenta. To trace the antigens, we conjugated fluorescent nanocrystals with Ag85A (Qdot-ITK-Ag85A). After inoculation in the pregnant mice, Qdot-ITK-Ag85A conjugates were detected in the liver, spleen of pregnant females and in all the fetuses and placentas examined. CONCLUSION: The fetal immune system could be primed in utero by mycobacterial antigens transported through the placenta.

Place, publisher, year, edition, pages
2010. Vol. 5, no 3, e9699- p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:su:diva-39175DOI: 10.1371/journal.pone.0009699ISI: 000275621000016PubMedID: 20300629OAI: oai:DiVA.org:su-39175DiVA: diva2:318977
Available from: 2010-05-12 Created: 2010-05-12 Last updated: 2017-12-12Bibliographically approved
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.
Keyword
Mucosal immunity, Vaccination, Diagnosis, Mycobacterial infection
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
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)
Opponent
Supervisors
Note
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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