title: OM-85 is an immunomodulator of interferon-β production and inflammasome activity.
abstract: The inflammasome-IL-1 axis and type I interferons (IFNs) have been shown to exert protective effects upon respiratory tract infections. Conversely, IL-1 has also been implicated in inflammatory airway pathologies such as asthma and chronic obstructive pulmonary disease (COPD). OM-85 is a bacterial extract with proved efficacy against COPD and recurrent respiratory tract infections, a cause of co-morbidity in asthmatic patients. We therefore asked whether OM-85 affects the above-mentioned innate immune pathways. Here we show that OM-85 induced interferon-β through the Toll-like receptor adaptors Trif and MyD88 in bone marrow-derived dendritic cells. Moreover, it exerted a dual role on IL-1 production; on the one hand, it upregulated proIL-1β and proIL-1α levels in a MyD88-dependent manner without activating the inflammasome. On the other hand, it repressed IL-1β secretion induced by alum, a well-known NLRP3 activator. In vivo, OM-85 diminished the recruitment of inflammatory cells in response to peritoneal alum challenge. Our findings therefore suggest that OM-85 favors a protective primed state, while dampening inflammasome activation in specific conditions. Taken together, these data bring new insights into the mechanisms of OM-85 action on innate immune pathways and suggest potential explanations for its efficacy in the treatment of virus-induced airway diseases.
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: A T
authors.initials: AT
authors.lastname: Dang
authors.affiliation: Vifor-Pharma c/o OM Pharma SA, 1217 Meyrin 1/Geneva, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Pasquali
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.|Present address: Roche Pharma (Schweiz) AG, Schönmattstrasse 2, 4153 Reinach, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Ludigs
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Guarda
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002457:Cell Extracts / Q000494:pharmacology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D010538:Peritonitis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D000095983:Bacterial Lysates
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000276:Adjuvants, Immunologic; D002457:Cell Extracts; D058847:Inflammasomes; D016899:Interferon-beta; D007375:Interleukin-1; D053594:Myeloid Differentiation Factor 88; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse