title: Non-FcεR bearing mast cells secrete sufficient interleukin-4 to control Francisella tularensis replication within macrophages.
abstract: Mast cells have classically been implicated in the triggering of allergic and anaphylactic reactions. However, recent findings have elucidated the ability of these cells to selectively release a variety of cytokines leading to bacterial clearance through neutrophil and dendritic cell mobilization, and suggest an important role in innate host defenses. Our laboratory has established a primary bone marrow derived mast cell-macrophage co-culture system and found that mast cells mediated a significant inhibition of Francisella tularensis live vaccine strain (LVS) uptake and replication within macrophages through contact and the secreted product interleukin-4 (IL-4). In this study, we utilized P815 mast cells and J774 macrophages to further investigate whether mast cell activation by non-FcεR driven signals could produce IL-4 and control intramacrophage LVS replication. P815 supernatants collected upon activation by the mast cell activating peptide MP7, as well as P815 cells co-cultured with J774 macrophages, exhibited marked inhibition of bacterial uptake and replication, which correlated with the production of IL-4. The inhibition noted in vitro was titratable and preserved at ratios relevant to cellular infiltration events following pulmonary challenge. Collectively, our data suggest that both primary mast cell and P815 mast cell (lacking FcεR) secreted IL-4 can control intramacrophage Francisella replication.
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Prea
authors.initials: P
authors.lastname: Thathiah
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sanapala
authors.forename: Annette R
authors.initials: AR
authors.lastname: Rodriguez
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.forename: Ashlesh K
authors.initials: AK
authors.lastname: Murthy
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Forsthuber
authors.forename: James P
authors.initials: JP
authors.lastname: Chambers
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005604:Francisella tularensis / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D014406:Tularemia / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4