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International journal of immunopathology and pharmacology

"FoxP3 Hunting" during infection with Francisella tularensis.


PMID 25572738

Abstract

Francisella tularensis is a Gram-negative intracellular bacterium that can cause acute disease in mouse models of infection when administered via the inhalational route. The immune response to a pulmonary infection is typified by an initial lack of pro-inflammatory cytokines, followed by hypercytokinemia prior to host death. It remains unclear what causes this delay in the host immune response. In this study we determine the presence of FoxP3 regulatory T cells in the lung, liver and spleen following intranasal infection with F. tularensis SCHU S4. In the lung, the site of initial infection, there is an increase in FoxP3+ cells during the first few days of infection and a notable absence of these cells at the point of cytokine storm and death (day 4 post-infection). This coincides with a decrease in the anti-inflammatory cytokine TGF-β and increases of chemokines MIP-1α, MIP-1β and RANTES. In our model, we also observed an overall decrease in the number of regulatory T cells in the spleen, which was not as evident in the liver. Overall, this data suggests that early on in an acute F. tularensis SCHUS4 infection regulatory T cells contribute to a dampening of the pro-inflammatory response, allowing for bacterial replication and spread.