title: Cell-contact dependent inhibition of monocytes by airway epithelial cells and reversion by infection with Respiratory Syncytial Virus.
abstract: Airway epithelial cells (AEC) are the first line of defense against airborne infectious microbes and play an important role in regulating the local immune response. However, the interplay of epithelial cells and professional immune cells during both homeostasis and infection has only been partially studied. The present study was performed to determine how bronchial epithelial cells affect the activation of monocytes. Under healthy conditions, AECs were shown to inhibit reactivity of monocytes. We hypothesized that upon infection, monocytes might be released from inhibition by AECs. We report that direct contact of monocytes with unstimulated BEAS2B epithelial cells results in inhibition of TNF secretion by activated monocytes. In addition to the known soluble modulators, we show that cell contacts between epithelial cells and monocytes or macrophages also contribute to homeostatic inhibitory actions. We find AECs to express the inhibitory molecule PD-L1 and blockade of PD-L1 results in increased secretion of pro-inflammatory cytokines from monocytes. Contrary to the inhibitory activities during homeostasis, epithelial cells infected with Respiratory Syncitial Virus (RSV) induce a significant release of inhibition. However, release of inhibition was not due to modulation of PD-L1 expression in AECs. We conclude that airway epithelial cells control the reactivity of monocytes through direct and indirect interactions; however tonic inhibition can be reverted upon stimulation of AECs with RSV and thereof derived molecular patterns. The study confirms the important role of airway epithelial cells for local immune reactions.
authors.affiliation: Faculté des Sciences et Technologie, Université Yahia Fares de Médéa, Algeria.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Oumouna
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weitnauer
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Germany.
authors.forename: Vedrana
authors.initials: V
authors.lastname: Mijošek
authors.affiliation: Institute of Pathology Heidelberg, German Center for Infection Research (DZIF), University Hospital Heidelberg, Germany.
authors.forename: Lotte M
authors.initials: LM
authors.lastname: Schmidt
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Eigenbrod
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Germany; Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Germany. Electronic address: alexander.dalpke@med.uni-heidelberg.de.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Dalpke
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen
keywords: Airways; Epithelial cells; Infection; Innate Immunity; Monocytes; Mucosal Immunology