OM-85 is an immunomodulator of interferon-\u03b2 production and inflammasome activity

A T Dang,K Ludigs,C Pasquali,G Guarda

doi:10.1038/srep43844

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.

Highlights

In models of pulmonary fibrosis and silicosis, a detrimental role for the NLRP3/IL-1 axis was witnessed[16,28,29,30,31,32,33,34,35,36,37,38,39]
These results suggest that OM-85 dampens selected inflammatory reactions, while potentiating innate immune defenses, two effects that might contribute to reducing infections and alleviating chronic obstructive pulmonary disease (COPD) and asthmatic conditions in the context of the respiratory tract
Whereas we did not observe significant inhibitory effects on IL-1αand IL-1βsecretion upon inflammasome triggering by ATP, we found that IL-1βsecretion induced by alum and – to a smaller extent by monosodium urate (MSU) – was downmodulated by OM-85 pre-treatment (Fig. 5a and Supplementary Figure 1a)

Summary

Introduction

In models of pulmonary fibrosis and silicosis, a detrimental role for the NLRP3/IL-1 axis was witnessed[16,28,29,30,31,32,33,34,35,36,37,38,39]. We asked whether OM-85 was an effective priming agent for multiple activators of the NLRP3 as well as for the AIM2 inflammasome, as both these platforms are important for detection of and protection from viral infections.

Results

Conclusion