title: Selective activation of human dendritic cells by OM-85 through a NF-kB and MAPK dependent pathway.
abstract: OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), a product made of the water soluble fractions of 21 inactivated bacterial strain patterns responsible for respiratory tract infections, is used for the prevention of recurrent upper respiratory tract infections and acute exacerbations in chronic obstructive pulmonary disease patients. OM-85 is able to potentiate both innate and adaptive immune responses. However, the molecular mechanisms responsible for OM-85 activation are still largely unknown. Purpose of this study was to investigate the impact of OM-85 stimulation on human dendritic cell functions. We show that OM-85 selectively induced NF-kB and MAPK activation in human DC with no detectable action on the interferon regulatory factor (IRF) pathway. As a consequence, chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) and B-cell activating cytokines (i.e. IL-6, BAFF and IL-10) were strongly upregulated. OM-85 also synergized with the action of classical pro-inflammatory stimuli used at suboptimal concentrations. Peripheral blood mononuclear cells from patients with COPD, a pathological condition often associated with altered PRR expression pattern, fully retained the capability to respond to OM-85. These results provide new insights on the molecular mechanisms of OM-85 activation of the immune response and strengthen the rational for its use in clinical settings.
authors.affiliation: Dept. Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Parola
authors.affiliation: Dept. Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Salogni
authors.affiliation: Dept. Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy.
authors.forename: Xenia
authors.initials: X
authors.lastname: Vaira
authors.affiliation: Dept. Public Health and Pediatric Sciences, Università degli Studi di Torino, Torino, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Scutera
authors.affiliation: Dept. Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Somma
authors.affiliation: Dept. Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Salvi
authors.affiliation: Dept. Public Health and Pediatric Sciences, Università degli Studi di Torino, Torino, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Musso
authors.affiliation: Pulmonary Division, Ospedale S. Giovanni Battista, Torino, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tabbia
authors.affiliation: Pulmonary Division, Ospedale S. Giovanni Battista, Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bardessono
authors.affiliation: Preclinical Research, OM Pharma SA, Meyrin 2/Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Pasquali
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Italy ; Dept. Biotechnology and Translational Medicine, Università degli Studi di Milano, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Dept. Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy ; Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.affiliation: Dept. Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bosisio
mesh_terms: D002457:Cell Extracts / Q000494:pharmacology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D006801:Humans; D050835:Interferon Regulatory Factors / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood; D015854:Up-Regulation; D000095983:Bacterial Lysates
chemical_list: D002457:Cell Extracts; D018925:Chemokines; D050835:Interferon Regulatory Factors; D016328:NF-kappa B; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates