“FoxP3 Hunting” during Infection with Francisella Tularensis

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 E tularensis 8CHU 84. 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-p and increases of chemokines MIP-l«, MIP-1P and RANTE8. 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 E tularensis 8CHU84 infection regulatory T cells contribute to a dampening of the pro-Inflammatory response, allowing for bacterial replication and spread.

In Vivo Intradermal Delivery of Bacteria by Using Microneedle Arrays

“…The spleen is especially affected during tularemia and becomes enlarged as a result of infiltrating inflammatory monocytes and neutrophils. The inflammatory infiltrates of the spleen lead to a shift in the ratio and relative percentages of monocytes, neutrophils, and T cells (19)(20)(21)(22)(23). Death ultimately results from system hypercytokinemia (21, 23).…”