<i>Mycobacterium vaccae</i>induces a strong Th1 response that subsequently declines in C57BL/6 mice

Abstract

<i>Mycobacterium (M.) vaccae</i> is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by <i>M. vaccae</i> isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain <i>M. bovis</i> Bacillus Calmette-Guérin (BCG) and isolated <i>M. vaccae</i> using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between <i>M. vaccae</i> and <i>M. bovis</i> BCG revealed that <i>M. vaccae</i> was more malignant than <i>M. bovis</i> in mice. We also demonstrated that serum from the <i>M. vaccae</i>-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by <i>M. vaccae</i> infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that <i>M. vaccae</i> infection increased the production of type I IFNs, which was associated with a reduced Th1 response.