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.

Immunity‐targeted approaches to the management of chronic and recurrent upper respiratory tract disorders in children

“…26 They act on both innate and adaptive immune responses, with recent findings supporting antiviral effects (eg increased interferon [IFN]-γ, IFN-α and IFN-β). [26][27][28] Interestingly, application of bacterial lysates also produces systemic effects, including increased serum immunoglobulin con- In this review, we want to highlight emerging, evidence-based approaches for conservative management of the most common recurrent and chronic URTIs in children, with an emphasis on the role of immunomodulation. clinicaltrials.gov; and Cochrane databases.…”

NLRP3 inflammasome: A likely target for the treatment of allergic diseases

“…Several inflammasomes, including NLRP1, NLRP3, NLRC4, and NLRP6, have been studied thus far . The NLR family pyrin domain containing 3 (NLRP3) is relevant for several human allergic disorders because its activation is associated with a range of allergic stimuli, such as silica, alum, and other allergens …”

Promising approaches for the treatment and prevention of viral respiratory illnesses

“…74,75 Mechanistic studies have confirmed pleiotropic immunomodulating effects on both innate and adaptive immunity. 76,77 Pidotimod, a synthetic dipeptide molecule, induces a variety of immunomodulatory effects 78,79 and has shown some efficacy in preventing RTIs, although this was not always confirmed. 80,81 Probiotic supplementation has been shown to reduce the incidence, duration, and severity of upper respiratory tract infections through immune modulation 82 and in particular rhinovirus infection through altering nasal innate inflammatory responses.…”