BALB/c mice display more enhanced BCG vaccine induced Th1 and Th17 response than C57BL/6 mice but have equivalent protection

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 95; no. 1; pp. 48 - 53
• Main Authors: Garcia-Pelayo, M. Carmen, Bachy, Véronique S, Kaveh, Daryan A, Hogarth, Philip J
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.01.2015
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antigens, Bacterial - immunology; Bacterial Proteins - immunology; Bacterial Proteins - pharmacology; BCG; BCG Vaccine - pharmacology; Cytokines - immunology; Female; Immunity, Cellular - drug effects; Immunity, Cellular - immunology; Infectious Disease; Mice, Inbred BALB C; Mice, Inbred C57BL; Mycobacterium bovis - immunology; Pulmonary/Respiratory; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; Th1; Th1 Cells - drug effects; Th1 Cells - immunology; Th17; Th17 Cells - drug effects; Th17 Cells - immunology; Tuberculosis; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - prevention & control; Tuberculosis, Splenic - immunology; Tuberculosis, Splenic - prevention & control; Vaccine; Vaccine; Tuberculosis; Th1; Th17; BCG
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2014.10.012

Summary It is generally assumed that the inbred mouse strains BALB/c ( H-2 d ) and C57BL/6 ( H-2 b ) respond to mycobacterial infection with distinct polarisation of T helper responses, with C57BL/6 predisposed to Th1 and BALB/c to Th2. We investigated this in a BCG-immunisation, Mycobacterium bovis challenge model. Following immunisation, lung and spleen cell cytokine responses to in vitro re-stimulation with a cocktail of seven secreted, immunogenic, recombinant mycobacterial proteins were determined. In both lung and spleen, BALB/c cells produced at least 2-fold more IFN-γ, and up to 7-fold more IL-2 and IL-17 than C57BL/6 cells, whereas IL-10 production was reciprocally increased in C57BL/6 mice. These data suggest that, contrary to reports in the literature, specific mycobacterial antigens are able to induce strong Th1 and Th17 responses in BALB/c mice following BCG vaccination, whilst in C57BL/6 mice, the Th1 response is partly counterbalanced by IL-10. After subsequent M. bovis low dose challenge, protection, as measured in the lungs and dissemination to the spleen, was equivalent in BALB/c and C57BL/6 mice, indicating that BCG-induced immunity was equivalent in both strains. Thus, the differential immune responses do not appear to have a role in protection, but further, as yet unidentified, specific immune responses play a significant role.