Direct and monocyte-induced innate immune response of human lung epithelial cells to Brucella abortus infection.
Although Brucella frequently infects humans through inhalation, its interaction with pulmonary cells has been overlooked. We examined whether human lung epithelial cells produce proinflammatory mediators in response to Brucella infection. Infection with smooth or rough strains of Brucella abortus induced the secretion of IL-8 and GM-CSF by the bronchial epithelial cell lines Calu-6 and 16HBE14o-, but not by the alveolar epithelial cell line A549. Infected Calu-6 cells also produced low levels of MCP-1. Since monocyte-derived cytokines may induce chemokine secretion in epithelial cells, cocultures of human monocytes (THP-1 cell line) and respiratory epithelial cells were used to study such interaction. IL-8 and MCP-1 levels in B. abortus-infected THP-1:A549 and THP-1:Calu-6 cocultures, and MCP-1 levels in THP-1:16HBE14o- cocultures, were higher than those detected in infected epithelial monocultures. Conditioned medium from infected monocytes induced the secretion of IL-8 and/or MCP-1 by A549 and Calu-6 cells, and these effects were mainly mediated by IL-1 (in A549 cells) or TNF-alpha (in Calu-6 cells). Conversely, culture supernatants from Brucella-infected bronchial epithelial cells induced MCP-1 production by monocytes, an effect largely mediated by GM-CSF. This study shows that human lung epithelial cells mount a proinflammatory response to Brucella, either directly or after interaction with Brucella-infected monocytes.
Ferrero
Mariana C
MC
Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioquímica, UBA, Junín 956 4to, Piso, 1113 Buenos Aires, Argentina.
Fossati
Carlos A
CA
Baldi
Pablo C
PC
D002003:Brucella abortus / Q000276:immunology*; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate; D009000:Monocytes / Q000276:immunology*
D017077:Culture Media, Conditioned; D016207:Cytokines