RIG-I/MDA5 activation upon Influenza D virus infection impairs the pro-inflammatory and antibacterial response triggered during secondary Mycoplasma bovis superinfection
Résumé
Pathogenic bacteria and viruses are often co-detected in cattle with respiratory illness. However, the clinical meaning of these bacterial/viral co-infections has long been controversial. Influenza D virus (IDV) is a novel member of the Orthomyxoviridae family that was discovered in 2011 and cattle is currently considered its primary host. In the last few years, IDV presence in bovine clinical samples has been associated with respiratory disease through metagenomic approaches and virological surveillance. Experimental in vivo challenge with IDV alone induced moderate respiratory signs in calves. However, when in co-infection with Mycoplasma bovis, IDV enhanced the bacterial colonization of the lower respiratory tract and worsened the gross lung lesions. In order to investigate the viral mechanisms inducing the aggravation of M. bovis bacterial superinfection, we used the organotypic ex vivo model Precision-Cut Lung Slices. Our results showed an impairment of pro-inflammatory and antibacterial responses following a primary IDV infection, with decreased production of several pro-inflammatory cytokines and chemokines, such as IL-1β, IL-8, CXCL10, IL-17, as well as inducible nitric oxid synthase, which are known to play an important role in counteracting bacterial infections. Stimulations with agonists of cytosolic helicases and TLR receptors revealed that a primary activation of RIG-I/MDA5 decreases the production of pro-inflammatory cytokines that are induced by TLR2 activation, similarly to what observed with the two replicating pathogens. Changes in the cellular ultrastructure of lung tissue following the co-infection were also investigated by electron microscopy studies. These data provide an interesting framework to better understand the dynamics of respiratory co-infections.