title: Analysis of the Caenorhabditis elegans innate immune response to Coxiella burnetii.
abstract: The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan. However, nematodes fed autoclave-killed CCB did not exhibit these symptoms. Although vertebrates detect C. burnetii via TLRs, pathologies in tol-1(-) mutant nematodes were indistinguishable from N2, and indicate nematodes do not employ this orthologue for detection of C. burnetii. sek-1(-) MAP kinase mutant nematodes succumbed to infection faster, suggesting that this signaling pathway plays a role in immune activation, as previously shown for orthologues in vertebrates during a C. burnetii infection. C. elegans daf-2(-) mutants are hyper-immune and exhibited significantly reduced pathological consequences during challenge. Collectively, these results demonstrate the utility of C. elegans for studying the innate immune response against C. burnetii and could lead to discovery of novel methods for prevention and treatment of disease in humans and livestock.
authors.affiliation: Program in Cellular, Molecular and Microbial Biology, Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Battisti
authors.affiliation: Program in Cellular, Molecular and Microbial Biology, Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Lance A
authors.initials: LA
authors.lastname: Watson
authors.affiliation: Program in Cellular, Molecular and Microbial Biology, Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Myo T
authors.initials: MT
authors.lastname: Naung
authors.affiliation: Program in Cellular, Molecular and Microbial Biology, Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Drobish
authors.affiliation: Program in Cellular, Molecular and Microbial Biology, Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Voronina
authors.affiliation: Program in Cellular, Molecular and Microbial Biology, Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Minnick
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D016997:Coxiella burnetii / Q000276:immunology*; D055786:Gene Knockout Techniques; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011778:Q Fever / Q000276:immunology*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C439300:Tol-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D048670:MAP Kinase Kinase 4; C516679:sek-1 protein, C elegans
keywords: Caenorhabditis elegans; Coxiella burnetii; Q fever; human pathogenic bacteria; immunity