THE IMPORTANCE OF IMMEDIATE LOCAL LUNG RESPONSE TO FRANCISELLA TULARENSIS PULMONARY INFECTION

Francisella tularensis is a gram negative facultative intracellular bacterium that can cause life-threatening infections in humans, and as such, is classified in the topmost category of agents that can serve for bio-terrorism. The extremely high virulence of F. tularemia was shown to be attributed to its systemic dissemination that leads to severe sepsis and extensive damage to the liver and spleen.

Vaccination of mice with Live Vaccine Strain (LVS) provides limited protection against pulmonary challenge with the virulent strains and diminishes significantly over time. To explore the mechanisms contributing to protective immune response to pulmonary F. tularensis infections we analyzed the host responses of LVS vaccinate mice following challenge with the highly virulent strain SchuS4.

We have found that "protected" mice (mice that received boost immunization) exhibit earlier cessation of bacterial growth, reduced bacterial burden and limited dissemination to systemic organs than "non-protected" mice (mice that received single immunization). In this system, we have demonstrated an earlier and higher magnitude of response of memory T cells within the lung of the "protected" mice after challenge. This response results in earlier activation of other resident cells and earlier expression of cytokines and adhesion molecules. In this fashion, lung resident memory T cells create a better anti-bacterial microenvironment in the lung tissue of the "protected" mice.

Establishment of methods by which one can fortify the early memory response within the lung is expected to bring about a significant mitigation of the deleterious effect of infection, and thus to effectively potentiate a coordinate immune response able to eradicate highly virulent pulmonary infections.