title: Mast cells inhibit intramacrophage Francisella tularensis replication via contact and secreted products including IL-4.
abstract: Francisella tularensis is an intracellular, Gram-negative bacterium that is the causative agent of pulmonary tularemia. The pathogenesis and mechanisms related to innate resistance against F. tularensis are not completely understood. Mast cells are strategically positioned within mucosal tissues, the major interface with the external environment, to initiate innate responses at the site of infection. Mast cell numbers in the cervical lymph nodes and the lungs progressively increased as early as 48 h after intranasal F. tularensis live vaccine strain (LVS) challenge. We established a primary bone marrow-derived mast cell-macrophage coculture system and found that mast cells significantly inhibit F. tularensis LVS uptake and growth within macrophages. Importantly, mice deficient in either mast cells or IL-4 receptor displayed greater susceptibility to the infection when compared with corresponding wild-type animals. Contact-dependent events and secreted products including IL-4 from mast cells, and IL-4 production from other cellular sources, appear to mediate the observed protective effects. These results demonstrate a previously unrecognized role for mast cells and IL-4 and provide a new dimension to our understanding of the innate immune mechanisms involved in controlling intramacrophage Francisella replication.
authors.affiliation: South Texas Center for Emerging Infectious Diseases, Department of Biology, University of Texas, San Antonio, TX 78249, USA.
authors.forename: Jyothi M
authors.initials: JM
authors.lastname: Ketavarapu
authors.forename: Annette R
authors.initials: AR
authors.lastname: Rodriguez
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Cong
authors.forename: Ashlesh K
authors.initials: AK
authors.lastname: Murthy
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Forsthuber
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.forename: Karl E
authors.initials: KE
authors.lastname: Klose
authors.forename: Michael T
authors.initials: MT
authors.lastname: Berton
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D002448:Cell Adhesion; D003260:Contact Inhibition; D004261:DNA Replication; D005604:Francisella tularensis / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism*; D042541:Intracellular Space / Q000382:microbiology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014406:Tularemia / Q000276:immunology / Q000382:microbiology
chemical_list: D001428:Bacterial Vaccines; D015847:Interleukin-4