Proteomic Analysis of Bronchoalveolar Lavage Fluid Proteins from Mice Infected with <i>Francisella tularensis</i> ssp. <i>novicida</i>

Abstract

<i>Francisella tularensis</i> causes the zoonosis tularemia in humans and is one of the most virulent bacterial pathogens. We utilized a global proteomic approach to characterize protein changes in bronchoalveolar lavage fluid from mice exposed to one of three organisms, <i>F. tularensis</i> ssp. <i>novicida</i>, an avirulent mutant of <i>F. tularensis</i> ssp. <i>novicida</i> (<i>F.t. novicida</i>-ΔmglA), and <i>Pseudomonas aeruginosa</i>. The composition of bronchoalveolar lavage fluid (BALF) proteins was altered following infection, including proteins involved in neutrophil activation, oxidative stress, and inflammatory responses. Components of the innate immune response were induced including the acute phase response and the complement system; however, the timing of their induction varied. <i>F. tularensis</i> ssp. <i>novicida</i> infected mice do not appear to have an effective innate immune response in the first hours of infection; however, within 24 h, they show an upregulation of innate immune response proteins. This delayed response is in contrast to <i>P. aeruginosa</i> infected animals which show an early innate immune response. Likewise, <i>F.t. novicida</i>-ΔmglA infection initiates an early innate immune response; however, this response is diminished by 24 h. Finally, this study identifies several candidate biomarkers, including Chitinase 3-like-1 (CHI3L1 or YKL-40) and peroxiredoxin 1, that are associated with <i>F. tularensis</i> ssp. <i>novicida</i> but not <i>P. aeruginosa</i> infection