Francisella tularensis is a highly virulent bacterium that causes tularemia, a 
disease that is often fatal if untreated. A live vaccine strain (LVS) of this 
bacterium is attenuated for virulence in humans but produces lethal disease in 
mice. F. tularensis has been classified as a Category A agent of bioterrorism. 
Despite this categorization, little is known about the components of the 
organism that are responsible for causing disease in its hosts. Here, we report 
the deletion of a well-characterized lipoprotein of F. tularensis, designated 
LpnA (also known as Tul4), in the LVS. An LpnA deletion mutant was comparable to 
the wild-type strain in its ability to grow intracellularly and cause lethal 
disease in mice. Additionally, mice inoculated with a sublethal dose of the 
mutant strain were afforded the same protection against a subsequent lethal 
challenge with the LVS as were mice initially administered a sublethal dose of 
the wild-type bacterium. The LpnA-deficient strain showed an equivalent ability 
to promote secretion of chemokines by human monocyte-derived macrophages as its 
wild-type counterpart. However, recombinant LpnA potently stimulated primary 
cultures of human macrophages in a Toll-like receptor 2-dependent manner. 
Although human endothelial cells were also activated by recombinant LpnA, their 
response was relatively modest. LpnA is clearly unnecessary for multiple 
functions of the LVS, but its inflammatory capacity implicates it and other 
Francisella lipoproteins as potentially important to the pathogenesis of 
tularemia.