Shaping the immune response to Francisella tularensis by the first infected cell (37.33)

Abstract

Abstract Francisella tularensis, the causative agent of tularemia, induces a host response that is dependent on the route of infection. Intranasal inoculations are more virulent and require fewer bacteria initially than an intradermal inoculation to produce a lethal infection (10^3 organisms in an intranasal inoculation versus 10^6 organisms in an intradermal inoculation). However, one day post infection, the bacterial load is similar in the spleen and lung regardless of the route of infection. This indicates that host response is specific to the infection site and that this response occurs within hours post infection. To test this hypothesis, 6-10 week old C57B6/J mice are given either intradermal or intranasal inoculations of live vaccine strain F. tularensis or fully virulent Schu S4 and, after four hours, the cell types are sorted by flow cytometry and examined to determine which cell populations are initially infected. Our initial results in the lung show that essentially all cells infected by four hours are alveolar macrophages, to the exclusion of other myeloid cells and lung parenchyma. To determine the important cytokines shaping the immune response, the alveolar macrophages are infected with F. tularensis in vitro and the cytokines the cells produce are analyzed. This will allow for targeted pharmacological alterations of the cytokine response and should influence the course of infection in vivo.