Persistent Bordetella bronchiseptica carriage is associated with broad phenotypic alterations of peripheral CD4+CD25+ T cells and differentially affects immune responses to secondary non-infectious and infectious stimuli in mice

The respiratory tract is constantly exposed to the environment and displays a favorable niche for colonizing microorganisms. However, the effects of respiratory bacterial carriage on the immune system and its implications for secondary responses remain largely unclear. We have employed respiratory carriage with Bordetella bronchiseptica (Bb) as the underlying model to comprehensively address effects on subsequent immune responses. Persistent carriage was associated with the stimulation of Bordetella-specific CD4+, CD8+ and CD4+CD25+Foxp3+ T cell responses and broad transcriptional activation was observed in CD4+CD25+ T cells. Importantly, transfer of lymphocytes from persistent carriers to acutely B. bronchiseptica infected mice resulted in a significantly increased bacterial burden in the recipient’s upper respiratory tract. In contrast, we found that B. bronchiseptica carriage resulted in a significant benefit for the host in systemic infection with Listeria monocytogenes. At the same time, vaccination and influenza A virus infection were unaffected. These data demonstrate that there are significant immune modulatory processes triggered by persistent B. bronchiseptica carriage that differentially affect subsequent immune responses. Thereby our results demonstrate the complexity of immune regulation induced by persistent bacterial carriage in the respiratory tract that can be beneficial or detrimental to the host, depending on the pathogen and the considered compartment. In total 8 sampels were analyzed. 7 and 42 days post Bb infection splenocytes from n = 6 BALB/c mice per group were pooled and CD4+CD25+ and CD4+CD25- T cells were FACS sorted. As controls the same cell subsets were isolated from age-matched uninfected control mice. For analysis each cell subset from Bb-infected mice was compared to the according uninfected control subset.