Abstract
We investigated whether the ability of commensal respiratory bacteria to modulate the innate immune response against bacterial and viral pathogens was a shared or strain-specific characteristic. Bacterial strains belonging to the Corynebacterium pseudodiphtheriticum and Dolosigranulum pigrum species were compared by studying their influence in the Toll-like receptor (TLR)-2- and TLR3-triggered immune responses in the respiratory tract, as well as in the resistance to Respiratory Syncytial Virus (RSV) and Streptococcus pneumoniae infections. We demonstrated that nasally administered C. pseudodiphteriticum 090104 or D. pigrum 040417 were able to modulate respiratory immunity and increase the resistance against pathogens, while other strains of the same species did not influence the respiratory immune responses, demonstrating a clear strain-dependent immunomodulatory effect of respiratory commensal bacteria. We also reported here that bacterium-like particles (BLP) and cell walls derived from immunomodulatory respiratory commensal bacteria are an interesting alternative for the modulation of the respiratory immune system. Our study is a step forward in the positioning of certain strains of respiratory commensal bacteria as next-generation probiotics for the respiratory tract.
Highlights
Respiratory infections are a common cause of morbidity and mortality
We aimed to evaluate the ability of the different respiratory commensal bacteria strains to modulate the lung inflammatory response triggered by TLR3 activation
TLR3 activation significantly increased the levels of Broncho-Alveolar Lavages (BAL) IFN-β, IFN-γ and IL-10 in all the experimental groups when compared to basal levels (Figure 1, Figure S1)
Summary
Respiratory infections are a common cause of morbidity and mortality. More than 4 million people die yearly as a consequence of acute respiratory infections worldwide [1]. It was reported that the direct interaction between RSV and S. pneumoniae induce modifications in the transcriptome of the bacterial pathogen leading to an enhanced expression of the virulence factors neuraminidase A/B and pneumolysin, potentiating the infectivity of pneumococci [5] Those findings highlight the complex interactions that exist between RSV and S. pneumoniae and the host, which must be efficiently regulated in order to diminish the severity and mortality of respiratory infections caused by these pathogens. In this regard, taking into consideration the increased antibiotic resistance of pneumococci and that the therapeutic possibilities for the treatment of viral infections are directed to reducing the symptoms but are not effective to fight off the virus; novel approaches to prevent respiratory infections and superinfections are urgently needed. We evaluated whether the viability of commensal respiratory bacteria was necessary to obtain the optimal beneficial effect on the respiratory innate immune response and the protection against pathogens
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