Abstract
Francisella tularensis (F. tularensis) is an intracellular pathogen that causes a potentially debilitating febrile illness known as tularemia. F. tularensis can be spread by aerosol transmission and cause fatal pneumonic tularemia. If untreated, mortality rates can be as high as 30%. To study the host responses to a live-attenuated tularemia vaccine, peripheral blood mononuclear cell (PBMC) samples were assayed from 10 subjects collected pre- and post-vaccination, using both the 2D-DIGE/MALDI-MS/MS and LC-MS/MS approaches. Protein expression related to antigen processing and presentation, inflammation (PPARγ nuclear receptor), phagocytosis, and gram-negative bacterial infection was enriched at Day 7 and/or Day 14. Protein candidates that could be used to predict human immune responses were identified by evaluating the correlation between proteome changes and humoral and cellular immune responses. Consistent with the proteomics data, parallel transcriptomics data showed that MHC class I and class II-related signals important for protein processing and antigen presentation were up-regulated, further confirming the proteomic results. These findings provide new biological insights that can be built upon in future clinical studies, using live attenuated strains as immunogens, including their potential use as surrogates of protection.
Highlights
Francisella tularensis (F. tularensis), a gram-negative coccobacillus, is an intracellular pathogen of humans and animals that causes a potentially debilitating febrile illness known as tularemia [1,2,3].F. tularensis infection occurs after exposure to infected wildlife species, or through bites from infected ticks and deer flies, and causes disease of varying severity dependent upon the portal of entry, the infectious dose, and the subspecies of the infecting strain [1,2,3,4]
peripheral blood mononuclear cell (PBMC) cell lysates from 10 subjects collected at pre-vaccination (Day 0) and post-vaccination (Days 7 and 14) with a live attenuated tularemia vaccine were assayed by two different laboratories
748 gel spots were identified for each 2D-DIGE gel, while 1872 proteins and 1517 protein families were identified in each sample when using LC-MS/MS (Tables S2–S8)
Summary
Francisella tularensis (F. tularensis), a gram-negative coccobacillus, is an intracellular pathogen of humans and animals that causes a potentially debilitating febrile illness known as tularemia [1,2,3].F. tularensis infection occurs after exposure to infected wildlife species (including rodents, hares and rabbits), or through bites from infected ticks and deer flies, and causes disease of varying severity dependent upon the portal of entry, the infectious dose, and the subspecies (biovar) of the infecting strain [1,2,3,4]. Francisella tularensis (F. tularensis), a gram-negative coccobacillus, is an intracellular pathogen of humans and animals that causes a potentially debilitating febrile illness known as tularemia [1,2,3]. The type A F. tularensis subspecies is the most infectious biovar (ID50 < 10 cfu), which is responsible for most cases of tularemia in North America. If untreated, this subspecies has mortality rates approaching 30% [3,4,5,6]. F. tularensis can be spread by aerosol transmission to cause fatal pneumonic tularemia and is classified as a Tier 1 select agent of bioterrorism, indicating its status as one of the most likely pathogens to be deliberately used in a bioterrorist attack [7,8]. Given the dangers of F. tularensis infection, more research on both the vaccination and molecular-level effects of F. tularensis on human health is needed [8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
