Francisella tularensis type B ΔdsbA mutant protects against type A strain and induces strong inflammatory cytokine and Th1-like antibody response in vivo

• Published in: Pathogens and disease 2015-11, Vol.73 (8), p.ftv058-ftv058
• Main Authors: Straskova, Adela, Spidlova, Petra, Mou, Sherry, Worsham, Patricia, Putzova, Daniela, Pavkova, Ivona, Stulik, Jiri
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibody Formation; Antibody response; Antigens; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Clonal deletion; Correlation analysis; Cross Protection; Cytokines - secretion; Deletion mutant; Disease Models, Animal; Female; Francisella tularensis; Francisella tularensis - classification; Francisella tularensis - enzymology; Francisella tularensis - immunology; Homology; Immunization; Immunology; Inflammation; Inflammatory response; Lymphocytes T; Mice, Inbred BALB C; Protein Disulfide-Isomerases - deficiency; Proteins; Th1 Cells - immunology; Tularemia; Tularemia - immunology; Tularemia - prevention & control; Vaccination; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Virulence Factors - deficiency
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1093/femspd/ftv058

Francisella tularensis subspecies tularensis is a highly virulent intracellular bacterial pathogen, causing the disease tularemia. However, a safe and effective vaccine for routine application against F. tularensis has not yet been developed. We have recently constructed the deletion mutants for the DsbA homolog protein (ΔdsbA/FSC200) and a hypothetical protein IglH (ΔiglH/FSC200) in the type B F. tularensis subsp. holarctica FSC200 strain, which exerted different protection capacity against parental virulent strain. In this study, we further investigated the immunological correlates for these different levels of protection provided by ΔdsbA/FSC200 and ΔiglH/FSC200 mutants. Our results show that ΔdsbA/FSC200 mutant, but not ΔiglH/FSC200 mutant, induces an early innate inflammatory response leading to strong Th1-like antibody response. Furthermore, vaccination with ΔdsbA/FSC200 mutant, but not with ΔiglH/FSC200, elicited protection against the subsequent challenge with type A SCHU S4 strain in mice. An immunoproteomic approach was used to map a spectrum of antigens targeted by Th1-like specific antibodies, and more than 80 bacterial antigens, including novel ones, were identified. Comparison of tularemic antigens recognized by the ΔdsbA/FSC200 post-vaccination and the SCHU S4 post-challenge sera then revealed the existence of 22 novel SCHU S4 specific antibody clones. This work is focused on characterization of immune response during in vivo infection of two attenuated Francisella tularensis mutant (ΔdsbA and ΔiglH) strains; importantly, the ΔdsbA mutant, but not the ΔiglH mutant, induced an early innate inflammatory response leading to strong Th1-like antibody response.