Peptidoglycan from Immunobiotic Lactobacillus rhamnosus Improves Resistance of Infant Mice to Respiratory Syncytial Viral Infection and Secondary Pneumococcal Pneumonia

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.

Viral strategies predisposing to respiratory bacterial superinfections

“…A similar protective effect against RSV‐pneumococcal superinfection, mediated by TLR‐3 activation, was observed in infant mice with the intranasal administration of viable, but also nonviable Lactobacillus rhamnosus or its purified peptidoglycan 101 . In addition, treatment of mice with anti‐IFN‐γ or anti‐IL‐10 monoclonal antibodies diminished their capacity to reduce lung bacterial cell counts and lung tissue injuries 102 . Factors expressed by commensal microbiota may provide additional protection against viral infections.…”

“…Conversely, changes in microbial community composition constitute a heightened element of risk towards viral respiratory infections and bacterial superinfections (Figure 4). 101,102 …”

New Progress Regarding the Use of Lactic Acid Bacteria as Live Delivery Vectors, Treatment of Diseases and Induction of Immune Responses in Different Host Species Focusing on Lactobacillus Species

“…Some LAB microbe-associated molecular patterns (MAMPs) are able of working together with the Toll-like receptor-2 (TLR2), TLR6 and nod-like receptors [94]. Moreover Lactobacillus salivarius JTB07 and Lactobacillus reuteri JTB07 have been reported to upregulate the expression of IL-12, IL-8, IL-6, and IL-1, while Lactobacillus acidophilus JTB05 to upregulate the interferon-gamma expression level of their host cells [45,158,164]. Lactobacillus salivarius UCC 118 and Lactobacillus johnsonii LJ-1 were reported to enhance the IgA response and phagocytic activity in head-kidney leucocytes [165].…”

“…In relationship with the protection against RSV-pneumococcal superinfection, the study revealed that peptidoglycan from Lactobacillus rhamnosus CRL1505. Considerably enhanced lung CD3+CD4+IFN-γ+, and CD3+CD4+IL-10+ T cells plus CD11c+Sigle cF+IFN-β+alveolar macrophages with the resulting of increases of IFN-γ, IL-10, and IFN-β in the respiratory tract [75,76]. Nasal administration of Lactobacillus rhamnosus CRL1505 strain to malnourished mice under recovery reduced quantitative and qualitative alterations of CD4+T cells in the bone marrow, thymus, spleen and lung as well, CRL1505 treatment increased Th2-cytokines; interleukin 10 and 4 in respiratory and systemic compartments [77].…”

Surviving Deadly Lung Infections: Innate Host Tolerance Mechanisms in the Pulmonary System

“…For example, it has been shown that intranasal administration of Lactobacillus rhamnosus can aid in resisting RSV infection in infant mice (239). Another study suggested that this was due to a priming effect, showing that nonviable L. rhamnosus or the bacterial cell wall component peptidoglycan can enhance inflammatory responses in a TLR3-dependent manner (240). In a similar manner, TLR3-dependent priming with the upper respiratory tract-resident species Corynebacterium pseudodiphtheriticum also improved the outcome of RSV and secondary S. pneumoniae infection (241).…”