Alveolar Macrophages Are Key Players in the Modulation of the Respiratory Antiviral Immunity Induced by Orally Administered Lacticaseibacillus rhamnosus CRL1505

Abstract

The oral administration of Lacticaseibacillus rhamnosus CRL1505 differentially modulates the respiratory innate antiviral immune response triggered by Toll-like receptor 3 (TLR3) activation in infant mice, improving the resistance to Respiratory Syncytial Virus (RSV) infection. In this work, by using macrophages depletion experiments and a detailed study of their production of cytokines and antiviral factors we clearly demonstrated the key role of this immune cell population in the improvement of both viral elimination and the protection against lung tissue damage induced by the CRL1505 strain. Orally administered L. rhamnosus CRL1505 activated alveolar macrophages and enhanced their ability to produce type I interferons (IFNs) and IFN-γ in response to RSV infection. Moreover, an increased expression of IFNAR1, Mx2, OAS1, OAS2, RNAseL , and IFITM3 was observed in alveolar macrophages after the oral treatment with L. rhamnosus CRL1505, which was consistent with the enhanced RSV clearance. The depletion of alveolar macrophages by the time of L. rhamnosus CRL1505 administration abolished the ability of infant mice to produce increased levels of IL-10 in response to RSV infection. However, no improvement in IL-10 production was observed when primary cultures of alveolar macrophages obtained from CRL1505-treated mice were analyzed. Of note, alveolar macrophages from the CRL1505 group had an increased production of IL-6 and IL-27 suggesting that these cells may play an important role in limiting inflammation and protecting lung function during RSV infection, by increasing the maturation and activation of Treg cells and their subsequent production of IL-10. In addition, we provided evidence of the important role of CD4 + cells and IFN-γ in the activation of alveolar macrophages highlighting a putative pathway through which the intestinal and respiratory mucosa are communicated under the influence of L. rhamnosus CRL1505.

The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

“…The albumin content in BAL was quantified as an indicator of the increased permeability of the bronchoalveolar capillary barrier [ 21 ]. In addition, lactate dehydrogenase (LDH) activity was quantified as an indicator of general cytotoxicity [ 22 ]. Albumin content was determined colorimetrically using a diagnostic kit (Wiener Lab, Buenos Aires, Argentina) that is based on the binding of albumin to bromocresol green.…”

Lactiplantibacillus plantarum as a Potential Adjuvant and Delivery System for the Development of SARS-CoV-2 Oral Vaccines

“…We have recently demonstrated that immunobiotics with the ability of modulating the respiratory immunity are able to functionally modulate the alveolar macrophages response to viral challenges. In fact, our results indicate that alveolar macrophages greatly contribute to the augment of IFN-γ and IFN-β in the respiratory tract of mice orally treated with L. rhamnosus CRL1505 [ 115 ] or L. plantarum MPL16 (submitted for publication). Moreover, an improved expression of IFNAR1, Mx2, OAS1, OAS2, RNAseL and IFITM3 in alveolar macrophages after the oral treatment with L. rhamnosus CRL1505 or L. plantarum MPL16 was detected in our experiments.…”

“…Not all lactobacilli strains possessing immunomodulatory abilities in the intestinal mucosa are capable of stimulating the respiratory immunity when orally administered [ 110 , 111 , 112 , 113 , 114 , 115 , 116 ]. Orally administered L. plantarum MPL16 but not L. plantarum CRL1506 was capable of modulating respiratory immunity.…”

“…The exact nature of the cellular and molecular signals used by orally administered immunobiotics to modulate the respiratory antiviral immunity remain to be determined. Our recent experiments blocking CD4 + T cells and IFN-γ allow the speculation of a potential mechanism that could explain the remote effect induced by orally administered immunobiotics [ 115 ]. The existence of the so-called common mucosal immune system implies that the immune cells activated in one mucosal tissue can mobilize and reach distant mucosal sites, where they can influence immune responses.…”

“…The existence of the so-called common mucosal immune system implies that the immune cells activated in one mucosal tissue can mobilize and reach distant mucosal sites, where they can influence immune responses. Then, the mobilization of B and T cells from the intestinal mucosa to the respiratory tract could be involved in the beneficial effects exerted by orally administered immunobiotics [ 85 , 115 ]. Strains such as L. plantarum MPL16 would induce the mobilization CD4 + IFN-γ + T cells from the intestine to the lungs, and the local production of IFN-γ would modulate the respiratory tract innate immune microenvironment, leading to the activation of local immune cells such as alveolar macrophages.…”