title: Murine splenocytes produce inflammatory cytokines in a MyD88-dependent response to Bacillus anthracis spores.
abstract: Bacillus anthracis is a sporulating Gram-positive bacterium that causes the disease anthrax. The highly stable spore is the infectious form of the bacterium that first interacts with the prospective host, and thus the interaction between the host and spore is vital to the development of disease. We focused our study on the response of murine splenocytes to the B. anthracis spore by using paraformaldehyde-inactivated spores (FIS), a treatment that prevents germination and production of products associated with vegetative bacilli. We found that murine splenocytes produce IL-12 and IFN-gamma in response to FIS. The IL-12 was secreted by CD11b cells, which functioned to induce the production of IFN-gamma by CD49b (DX5) NK cells. The production of these cytokines by splenocytes was not dependent on TLR2, TLR4, TLR9, Nod1, or Nod2; however, it was dependent on the signalling adapter protein MyD88. Unlike splenocytes, Nod1- and Nod2-transfected HEK cells were activated by FIS. Both IL-12 and IFN-gamma secretion were inhibited by treatment with B. anthracis lethal toxin. These observations suggest that the innate immune system recognizes spores with a MyD88-dependent receptor (or receptors) and responds by secreting inflammatory cytokines, which may ultimately aid in resisting infection.
authors.affiliation: Institut Pasteur, Unité des Toxines et Pathogénie Bactérienne, Paris, F-75015, France.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Glomski
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Fritz
authors.forename: Selina J
authors.initials: SJ
authors.lastname: Keppler
authors.forename: Viviane
authors.initials: V
authors.lastname: Balloy
authors.forename: Michel
authors.initials: M
authors.lastname: Chignard
authors.forename: Michèle
authors.initials: M
authors.lastname: Mock
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Goossens
mesh_terms: D000818:Animals; D001408:Bacillus anthracis / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology*; D013171:Spores, Bacterial / Q000276:immunology*
chemical_list: D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic