Abstract
Several research works have demonstrated that beneficial microbes with the capacity to modulate the mucosal immune system (immunobiotics) are an interesting alternative to improve the outcome of bacterial and viral respiratory infections. Among the immunobiotic strains with the capacity to beneficially modulate respiratory immunity, Lactobacillus rhamnosus CRL1505 has outstanding properties. Although we have significantly advanced in demonstrating the capacity of L. rhamnosus CRL1505 to improve resistance against respiratory infections as well as in the cellular and molecular mechanisms involved in its beneficial activities, the potential protective ability of this strain or its immunomodulatory cellular fractions in the context of a secondary bacterial pneumonia has not been addressed before. In this work, we demonstrated that the nasal priming with non-viable L. rhamnosus CRL1505 or its purified peptidoglycan differentially modulated the respiratory innate antiviral immune response triggered by toll-like receptor 3 activation in infant mice, improving the resistance to primary respiratory syncytial virus (RSV) infection, and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, we found that peptidoglycan from L. rhamnosus CRL1505 significantly improved lung CD3+CD4+IFN-γ+, and CD3+CD4+IL-10+ T cells as well as CD11c+SiglecF+IFN-β+ alveolar macrophages with the consequent increases of IFN-γ, IL-10, and IFN-β in the respiratory tract. Our results also showed that the increase of these three cytokines is necessary to achieve protection against respiratory superinfection since each of them are involved in different aspect of the secondary pneumococcal pneumonia that have to be controlled in order to reduce the severity of the infectious disease: lung pneumococcal colonization, bacteremia, and inflammatory-mediated lung tissue injury.
Highlights
Respiratory viral attack often result in mild to moderate infection; life-threatening disease can occur in high-risk populations such as infants, elderly, and immunocompromised hosts
We have previously demonstrated that nasal administration of non-viable L. rhamnosus CRL1505 (HK1505) reduced lung injuries triggered by Toll-like receptor 3 (TLR3) activation (13)
We aimed to evaluate the effect of the nasal priming with the peptidoglycan from L. rhamnosus CRL1505 (PG1505) on the immune response triggered by the viral pathogen-associated molecular pattern poly(I:C) and compare it with the effect induced by HK1505
Summary
Respiratory viral attack often result in mild to moderate infection; life-threatening disease can occur in high-risk populations such as infants, elderly, and immunocompromised hosts. Secondary bacterial pneumonia is an important complication responsible for high morbidity and mortality during epidemic and pandemic viral respiratory infections in infants and children (1–3). Numerous studies have investigated how primary influenza virus (IFV) infection enhances the susceptibility to secondary pneumococcal disease, by increasing bacterial attachment and colonization, disrupting epithelial barriers, and altering the innate immune response in the respiratory tract (3). IFV and S. pneumoniae interaction has been extensively studied because of its great impact in the severity of respiratory infections, other viruses like the Respiratory Syncytial Virus (RSV) have been associated to an increased susceptibility to secondary pneumococcal pneumonia
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