title: Inflammasome priming is similar for francisella species that differentially induce inflammasome activation.
abstract: Inflammasome activation is a two-step process where step one, priming, prepares the inflammasome for its subsequent activation, by step two. Classically step one can be induced by LPS priming followed by step two, high dose ATP. Furthermore, when IL-18 processing is used as the inflammasome readout, priming occurs before new protein synthesis. In this context, how intracellular pathogens such as Francisella activate the inflammasome is incompletely understood, particularly regarding the relative importance of priming versus activation steps. To better understand these events we compared Francisella strains that differ in virulence and ability to induce inflammasome activation for their relative effects on step one vs. step two. When using the rapid priming model, i.e., 30 min priming by live or heat killed Francisella strains (step 1), followed by ATP (step 2), we found no difference in IL-18 release, p20 caspase-1 release and ASC oligomerization between Francisella strains (F. novicida, F. holarctica -LVS and F. tularensis Schu S4). This priming is fast, independent of bacteria viability, internalization and phagosome escape, but requires TLR2-mediated ERK phosphorylation. In contrast to their efficient priming capacity, Francisella strains LVS and Schu S4 were impaired in inflammasome triggering compared to F. novicida. Thus, observed differences in inflammasome activation by F. novicida, LVS and Schu S4 depend not on differences in priming but rather on their propensity to trigger the primed inflammasome.
authors.affiliation: Davis Heart & Lung Research Institute and Pulmonary Allergy Critical Care and Sleep Medicine Division, The Ohio State University, Columbus, OH, 43210, United States of America; Microbiology and Immunology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors.forename: Mohammed G
authors.initials: MG
authors.lastname: Ghonime
authors.affiliation: Davis Heart & Lung Research Institute and Pulmonary Allergy Critical Care and Sleep Medicine Division, The Ohio State University, Columbus, OH, 43210, United States of America.
authors.forename: Srabani
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Microbiology and Immunology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors.forename: Ramadan A
authors.initials: RA
authors.lastname: Eldomany
authors.affiliation: Davis Heart & Lung Research Institute and Pulmonary Allergy Critical Care and Sleep Medicine Division, The Ohio State University, Columbus, OH, 43210, United States of America.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
authors.affiliation: Davis Heart & Lung Research Institute and Pulmonary Allergy Critical Care and Sleep Medicine Division, The Ohio State University, Columbus, OH, 43210, United States of America.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Gavrilin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005603:Francisella / Q000145:classification* / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D050296:Microbial Viability; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D010766:Phosphorylation; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014774:Virulence
chemical_list: D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D020382:Interleukin-18; C402202:PYCARD protein, human; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D000255:Adenosine Triphosphate