title: Mycobacterium bovis bacilli Calmette-Guerin regulates leukocyte recruitment by modulating alveolar inflammatory responses.
abstract: Leukocyte migration into the epithelial compartment is an important feature in the active phase of mycobacterial infections. In this study, we used the Transwell model to investigate the mechanisms behind mycobacteria-induced leukocyte recruitment and investigated the role of TLR2 and TLR4 in this process. Infection of epithelial cells resulted in significantly increased secretion of the neutrophil chemotactic CXCL8 and IL-6, but no secretion of monocyte chemotactic CCL2 or TNF-α was observed. In contrast to epithelial response, mycobacteria-infected neutrophils and monocytes secreted all these cytokines. Corresponding with epithelial cytokine response, mycobacterial infection of the epithelial cells increased neutrophil diapedesis, but decreased monocyte recruitment. However, monocyte recruitment towards mycobacteria infected epithelial cells significantly increased following addition of neutrophil pre-conditioned medium. Mycobacterial infection also increases alveolar epithelial expression of TLR2, but not TLR4, as analyzed by flow cytometry, Western blotting and visualized by confocal microscopy. Blocking of TLR2 inhibited neutrophil recruitment and cytokine secretion, while blocking of TLR4 had a lesser effect. To summarize, we found that primary alveolar epithelial cells produced a selective TLR2-dependent cytokine secretion upon mycobacterial infection. Furthermore, we found that cooperation between cells of the innate immunity is required in mounting proper antimicrobial defence.
authors: Department of Microbiology Immunology and Glycobiology, Division of Laboratory Medicine, Lund University, Lund, Sweden.
authors: Märta
authors: M
authors: Andersson
authors: Nataliya
authors: N
authors: Lutay
authors: Oscar
authors: O
authors: Hallgren
authors: Gunilla
authors: G
authors: Westergren-Thorsson
authors: Majlis
authors: M
authors: Svensson
authors: Gabriela
authors: G
authors: Godaly
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4