Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection

Abstract

BackgroundSome studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before.ObjectiveThe aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection.ResultsNasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains.ConclusionsThe present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible to beneficially modulate the respiratory defenses against RSV by using heat-killed immunobiotics.

Nasal priming with immunobiotic Lactobacillus rhamnosus modulates inflammation–coagulation interactions and reduces influenza virus-associated pulmonary damage

“…These results are in line with previous reports of our group using this strain in the context of pulmonary infections with other pathogens [11,21,38,39]. The delicate balance between pro-inflammatory cytokines and anti-inflammatory cytokines is pivotal for a proper and regulated immune response.…”

“…In previous studies using poly(I:C) (a dsRNA analog) as model for RNA virus infections, we reported the modulation of pro-inflammatory and regulatory cytokines, as well as certain IFN molecules by administration of Lr1505 [21]. In this study, we use a similar approach to evaluate the actual effect of Lr1505 in the context of an IFV infection.…”

“…Based on previous results using the immunobiotic strain L. rhamnosus CRL1505 for enhancing antiviral immunity against RSV and modulating inflammation [21,28], we explored the effectiveness of this strain (alive or heatkilled) to reduce the influenza burden of disease. IFV-infected mice receiving Lr1505 or HK-Lr1505 showed a milder disease course than non-treated mice, and presented a significantly higher survival rate.…”

The Fecal Microbiota Profile and Bronchiolitis in Infants

“…Although data are scarce, murine studies have deciphered the relationship of gut microbiota with host response against viral ARIs (eg, influenza, RSV). [34][35][36] For instance, Ichinohe et al, 34 using an antibiotic-treated mouse model, reported that a disruption of gut microbiota (ie, dysbiosis) impairs the generation of virusspecific CD4 and CD8 T cells and antibody responses after influenza virus infection, suggesting the need for an intact commensal bacterial community in the establishment of immune response against viral ARIs. Our study corroborates these earlier findings and extends them by demonstrating the association of Bacteroides-dominant fecal microbiota profiles with bronchiolitis in infants.…”

Caracterização molecular da comunidade bacteriana em rebanhos leiteiros com mastite subclínica

“…Propionibacterium granulosum é encontrado nas mesmas condições, mas em menor abundância do que as espécies de P. acnes (PERRY et al, 2011 VILLENA et al, 20012;TOMOSADA et al, 2013). Dessa forma, os resultados aqui apresentados demonstram que são necessárias mais investigações para um melhor entendimento de como os patógenos bacterianos podem influenciar a comunidade normal do sistema mamário.…”