The Ability of Postimmunobiotics from L. rhamnosus CRL1505 to Protect against Respiratory Syncytial Virus and Pneumococcal Super-Infection Is a Strain-Dependent Characteristic

Fernanda Raya Tonetti; Patricia Clua; Kohtaro Fukuyama; Guillermo Marcial; Jacinto Sacur; Gabriela Marranzino; Mikado Tomokiyo; Guadalupe Vizoso-Pinto; Apolinaria Garcia-Cancino; Shoichiro Kurata; Haruki Kitazawa; Julio Villena

doi:10.3390/microorganisms10112185

The Ability of Postimmunobiotics from L. rhamnosus CRL1505 to Protect against Respiratory Syncytial Virus and Pneumococcal Super-Infection Is a Strain-Dependent Characteristic

Microorganisms. 2022 Nov 3;10(11):2185. doi: 10.3390/microorganisms10112185.

Authors

Affiliations

¹ Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucumán 4000, Argentina.
² Laboratory of Animal Food Function, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
³ Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
⁴ Infection Biology Laboratory, Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, Tucuman 4000, Argentina.
⁵ Facultad de Ciencias de la Salud, Universidad del Norte Santo Tomás de Aquino (UNSTA), Tucumán 4000, Argentina.
⁶ Laboratory of Bacterial Pathogenicity, Faculty of Biological Sciences, University of Concepcion, Concepcion 4030000, Chile.
⁷ Laboratory of Molecular Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.

Abstract

Previously, we demonstrated that the non-viable strain Lacticaseibacillus rhamnosus CRL1505 (NV1505) or its purified peptidoglycan (PG1505) differentially modulated the respiratory innate antiviral immune response triggered by Toll-like receptor (TLR)-3 activation in infant mice, improving the resistance to primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. In this work, we evaluated the effect of other non-viable L. rhamnosus strains and their peptidoglycans on the respiratory immune response and their impact on primary and secondary respiratory infections. In addition, the duration of the protective effect induced by NV1505 and PG1505 as well as their ability to protect against different Streptococcus pneumoniae serotypes were evaluated. Our results showed that among the five selected L. rhamnosus strains (CRL1505, CRL498, CRL576, UCO25A and IBL027), NV1505 and NVIBL027 improved the protection against viral and pneumococcal infections by modulating the respiratory immune response. Of note, only the PG1505 presented immunomodulatory activities when compared with the other purified peptidoglycans. Studies on alveolar macrophages showed that NV1505 and PG1505 differentially modulated the expression of IL-6, IFN-γ, IFN-β, TNF-α, OAS1, RNAseL and IL-27 genes in response to RSV infection, and IL-6, IFN-γ, IL-1β, TNF-α, CCL2, CXCL2, CXCL10 and IL-27 in response to pneumococcal challenge. Furthermore, we demonstrated that NV1505 and PG1505 treatments protected mice against secondary pneumococcal pneumonia produced by different serotypes of S. pneumoniae until 30 days after stimulation with poly(I:C). This work advances the characterization of the protective effect of NV1505 and PG1505 by demonstrating that they increase resistance against the pneumococcal serotypes 3, 6B, 14 and 19F, with an effect that lasts up to 30 days after the primary viral inflammation. The results also confirm that the immunomodulatory properties of NV1505 and PG1505 are unique and are not shared by other members of this species, and suggest the existence of a capacity to stimulate trained immunity in alveolar macrophages.

Keywords: Lacticaseibacillus rhamnosus CRL1505; Streptococcus pneumoniae; TLR3; antiviral immunity; peptidoglycan; respiratory superinfection; respiratory syncytial virus.

Abstract

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