OM-85 is an immunomodulator of interferon-β production and inflammasome activity.

Details

Ressource 1Download: srep43844.pdf (974.77 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_8B66392D35BF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
OM-85 is an immunomodulator of interferon-β production and inflammasome activity.
Journal
Scientific reports
Author(s)
Dang A.T., Pasquali C., Ludigs K., Guarda G.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
06/03/2017
Peer-reviewed
Oui
Volume
7
Pages
43844
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
Adaptor Proteins, Vesicular Transport/genetics, Adaptor Proteins, Vesicular Transport/metabolism, Adjuvants, Immunologic/pharmacology, Animals, Bone Marrow Cells/drug effects, Bone Marrow Cells/metabolism, Cell Extracts/pharmacology, Cells, Cultured, Dendritic Cells/drug effects, Dendritic Cells/metabolism, Inflammasomes/drug effects, Inflammasomes/metabolism, Interferon-beta/metabolism, Interleukin-1/metabolism, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88/genetics, Myeloid Differentiation Factor 88/metabolism, Peritonitis/genetics, Peritonitis/metabolism, Peritonitis/prevention & control
Pubmed
Web of science
Open Access
Yes
Create date
14/03/2017 11:55
Last modification date
20/08/2019 15:50
Usage data