Stanislas Grassin-Delyle1,2, Charlotte Abrial3, Hélène Salvator4,3, Marion Brollo3, Emmanuel Naline4,3, Philippe Devillier4,3. 1. Département des Maladies Respiratoires, Hôpital Foch, Suresnes, France, stanislas.grassin-delyle@uvsq.fr. 2. INSERM UMR 1173 et Plateforme de spectrométrie de masse MasSpecLab, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint Quentin, Université Paris Saclay, Montigny-le-Bretonneux, France, stanislas.grassin-delyle@uvsq.fr. 3. Laboratoire de Pharmacologie UPRES EA220, Université Versailles Saint Quentin, Université Paris Saclay, Hôpital Foch, Suresnes, France. 4. Département des Maladies Respiratoires, Hôpital Foch, Suresnes, France.
Abstract
BACKGROUND: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. METHODS: Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. RESULTS: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. CONCLUSIONS: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype. The Author(s). Published by S. Karger AG, Basel.
BACKGROUND: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. METHODS:Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. RESULTS: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. CONCLUSIONS: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype. The Author(s). Published by S. Karger AG, Basel.
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