CD1d-dependent natural killer T (NKT) cells play an important protective role in a variety of autoimmune, allergic, tumor, and infectious diseases, but there are several controversial reports. The balance in subsets of NKT cells and their activation status prior to induction of such diseases could play a critical role in the clinical outcome. Pasteurella pneumotropica is a commonly found bacterium in laboratory rodents. Because this infection is often asymptomatic and hence can go undetected,

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... d given different levels of acceptable health status in different animal facilities, this infection could impact the outcome of reported scientific studies. We report that subclinical natural infection with P. pneumotropica significantly affects the balance among different subsets of NKT cells. While the major CD1ddependent population, i.e., CD4 + NKT cells, was not significantly affected by infection in wild-type (WT) or CD1d -/mice, CD8 + NKT cells significantly increased in infected WT mice. Interestingly, double negative NKT cells, while significantly suppressed in WT mice due to infection, were unaffected in CD1d -/mice. The pattern of proinflammatory cytokines IFN-γ and IL-17A considerably changed as a result of infection. The differential effects were even more pronounced when investigating different T-cell subsets and their cytokine profiles. While the effect of infection on shaping immune cell balance could be expected, mice lacking CD1d-dependent NKT cells differed entirely in their response to a subclinical infection. This subsequently indicated influences of NKT cells on other T-cell subsets and their cytokine milieu. Collectively, these data confirm the importance of controlling environmental factors which could have strong impacts on immune balance, and consequently dictate the outcome of immune-mediated diseases.