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Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis

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Beltrán-Beck, Beatriz and de la Fuente, José and Garrido, Joseba M and Aranaz Martín, Alicia and Sevilla, Iker and Villar, Margarita and Boadella, Mariana and Galindo, Ruth C and Pérez de la Lastra, José M and Moreno Cid, Juan A and Fernández de Mera, Isabel G and Alberdi, Pilar and Santos, Gracia and Ballesteros, Cristina and Lyashchenko, Konstantin P and Minguijón, Esmeralda and Romero Martínez, Beatriz and Juan Ferré, Lucía de and Domínguez Rodríguez, Lucas and Juste, Ramón and Gortazar, Christian (2014) Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis. PLoS ONE, 9 (5). e98048. ISSN 1932-6203

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Official URL: http://dx.doi.org/10.1371/journal.pone.0098048



Abstract

Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.


Item Type:Article
Subjects:Medical sciences > Veterinary
ID Code:39636
Deposited On:20 Dec 2016 11:17
Last Modified:20 Dec 2016 11:17

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