Non-FcεR bearing mast cells secrete sufficient interleukin-4 to control Francisella tularensis replication within macrophages

• Published in: Cytokine (Philadelphia, Pa.) Vol. 55; no. 2; pp. 211 - 220
• Main Authors: Thathiah, Prea, Sanapala, Shilpa, Rodriguez, Annette R., Yu, Jieh-Juen, Murthy, Ashlesh K., Guentzel, M. Neal, Forsthuber, Thomas G., Chambers, James P., Arulanandam, Bernard P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2011
• Subjects: anaphylaxis; Animals; bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Bone Marrow Cells - physiology; Cells, Cultured; coculture; Coculture Techniques; Francisella tularensis; Francisella tularensis - immunology; Francisella tularensis - physiology; IL-4; Innate immunity; interleukin-4; Interleukin-4 - secretion; macrophages; Macrophages - cytology; Macrophages - immunology; Macrophages - microbiology; Mast cells; Mast Cells - cytology; Mast Cells - immunology; Mast Cells - secretion; Mice; Mice, Inbred C57BL; Receptors, IgE - genetics; Receptors, IgE - immunology; Respiratory infection; Tularemia - immunology; Tumor Necrosis Factor-alpha - immunology; IL-4; Innate immunity; Mast cells; Respiratory infection; Francisella tularensis
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2011.04.009

► We utilize P815 mast cells and J774 macrophages as surrogates for primary mast cells and macrophages respectively. ► Mast cell activation by non-FcεR driven signals produces IL-4 and control intramacrophage LVS replication. ► Inhibition in vitro is preserved at ratios relevant to cellular infiltration following pulmonary challenge. 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.