Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae

Autores
Fukuyama, Kohtaro; Cisterna Vergara, Solange; Baillo, Ayelen Antonella; Lorenzo Pisarello, Maria Jose; Gong, Weichen; Nishiyama, Keita; Villena, Julio Cesar; Kitazawa, Haruki
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Respiratory bacterial infections represent a major health challenge in swineproduction, highlighting the need for novel immunomodulatory strategies that enhancehost resistance. In this study, we investigated whether porcine intestinal lactobacilli couldmodulate the gut–lung axis and improve respiratory innate immunity in a mouse model ofStreptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) wereorally administered to Swiss mice prior to pneumococcal challenge. The resistance tothe infection, the lung damage and the respiratory innate immune response were evaluated. Results: Only strain LAFF998 significantly reduced pulmonary bacterial loads,prevented bacteremia, and attenuated lung injury. This protective effect was associatedwith selective modulation of respiratory immunity, characterized by reduced neutrophilicinflammation, increased lymphocyte recruitment, and enhanced activation of alveolarmacrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-β, IFN-γ, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages fromLAFF998-treated mice exhibited a primed phenotype with heightened cytokine responsesto pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to conferprotection or significantly modulate respiratory immune responses. Conclusions: Thesefindings demonstrate a strict strain-dependent effect among porcine L. salivarius isolatesand identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innateimmunity through the gut–lung axis. This work supports further studies of LAFF998 as animmunobiotic strategy for the prevention of respiratory infections in pigs.
Fil: Fukuyama, Kohtaro. Tohoku University; Japón
Fil: Cisterna Vergara, Solange. Tohoku University; Japón
Fil: Baillo, Ayelen Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
Fil: Lorenzo Pisarello, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
Fil: Gong, Weichen. Tohoku University; Japón
Fil: Nishiyama, Keita. Tohoku University; Japón
Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; Japón
Fil: Kitazawa, Haruki. Tohoku University; Japón
Materia
Ligilactobacillus salivarius LAFF998
immunobiotic
gut-lung axis
respiratory immunity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/290132
Acceder
id CONICETDig_a6e6bcd992a2f7c29919adcbed4fe987
oai_identifier_str oai:ri.conicet.gov.ar:11336/290132
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniaeFukuyama, KohtaroCisterna Vergara, SolangeBaillo, Ayelen AntonellaLorenzo Pisarello, Maria JoseGong, WeichenNishiyama, KeitaVillena, Julio CesarKitazawa, HarukiLigilactobacillus salivarius LAFF998immunobioticgut-lung axisrespiratory immunityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Respiratory bacterial infections represent a major health challenge in swineproduction, highlighting the need for novel immunomodulatory strategies that enhancehost resistance. In this study, we investigated whether porcine intestinal lactobacilli couldmodulate the gut–lung axis and improve respiratory innate immunity in a mouse model ofStreptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) wereorally administered to Swiss mice prior to pneumococcal challenge. The resistance tothe infection, the lung damage and the respiratory innate immune response were evaluated. Results: Only strain LAFF998 significantly reduced pulmonary bacterial loads,prevented bacteremia, and attenuated lung injury. This protective effect was associatedwith selective modulation of respiratory immunity, characterized by reduced neutrophilicinflammation, increased lymphocyte recruitment, and enhanced activation of alveolarmacrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-β, IFN-γ, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages fromLAFF998-treated mice exhibited a primed phenotype with heightened cytokine responsesto pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to conferprotection or significantly modulate respiratory immune responses. Conclusions: Thesefindings demonstrate a strict strain-dependent effect among porcine L. salivarius isolatesand identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innateimmunity through the gut–lung axis. This work supports further studies of LAFF998 as animmunobiotic strategy for the prevention of respiratory infections in pigs.Fil: Fukuyama, Kohtaro. Tohoku University; JapónFil: Cisterna Vergara, Solange. Tohoku University; JapónFil: Baillo, Ayelen Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Lorenzo Pisarello, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Gong, Weichen. Tohoku University; JapónFil: Nishiyama, Keita. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Kitazawa, Haruki. Tohoku University; JapónMultidisciplinary Digital Publishing Institute2026-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/290132Fukuyama, Kohtaro; Cisterna Vergara, Solange; Baillo, Ayelen Antonella; Lorenzo Pisarello, Maria Jose; Gong, Weichen; et al.; Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae; Multidisciplinary Digital Publishing Institute; Animals; 16; 5; 3-2026; 1-152076-2615CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-2615/16/5/825info:eu-repo/semantics/altIdentifier/doi/10.3390/ani16050825info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:40:18Zoai:ri.conicet.gov.ar:11336/290132instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 14:40:19.203CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
title Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
spellingShingle Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
Fukuyama, Kohtaro
Ligilactobacillus salivarius LAFF998
immunobiotic
gut-lung axis
respiratory immunity
title_short Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
title_full Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
title_fullStr Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
title_full_unstemmed Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
title_sort Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
dc.creator.none.fl_str_mv Fukuyama, Kohtaro
Cisterna Vergara, Solange
Baillo, Ayelen Antonella
Lorenzo Pisarello, Maria Jose
Gong, Weichen
Nishiyama, Keita
Villena, Julio Cesar
Kitazawa, Haruki
author Fukuyama, Kohtaro
author_facet Fukuyama, Kohtaro
Cisterna Vergara, Solange
Baillo, Ayelen Antonella
Lorenzo Pisarello, Maria Jose
Gong, Weichen
Nishiyama, Keita
Villena, Julio Cesar
Kitazawa, Haruki
author_role author
author2 Cisterna Vergara, Solange
Baillo, Ayelen Antonella
Lorenzo Pisarello, Maria Jose
Gong, Weichen
Nishiyama, Keita
Villena, Julio Cesar
Kitazawa, Haruki
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ligilactobacillus salivarius LAFF998
immunobiotic
gut-lung axis
respiratory immunity
topic Ligilactobacillus salivarius LAFF998
immunobiotic
gut-lung axis
respiratory immunity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Respiratory bacterial infections represent a major health challenge in swineproduction, highlighting the need for novel immunomodulatory strategies that enhancehost resistance. In this study, we investigated whether porcine intestinal lactobacilli couldmodulate the gut–lung axis and improve respiratory innate immunity in a mouse model ofStreptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) wereorally administered to Swiss mice prior to pneumococcal challenge. The resistance tothe infection, the lung damage and the respiratory innate immune response were evaluated. Results: Only strain LAFF998 significantly reduced pulmonary bacterial loads,prevented bacteremia, and attenuated lung injury. This protective effect was associatedwith selective modulation of respiratory immunity, characterized by reduced neutrophilicinflammation, increased lymphocyte recruitment, and enhanced activation of alveolarmacrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-β, IFN-γ, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages fromLAFF998-treated mice exhibited a primed phenotype with heightened cytokine responsesto pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to conferprotection or significantly modulate respiratory immune responses. Conclusions: Thesefindings demonstrate a strict strain-dependent effect among porcine L. salivarius isolatesand identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innateimmunity through the gut–lung axis. This work supports further studies of LAFF998 as animmunobiotic strategy for the prevention of respiratory infections in pigs.
Fil: Fukuyama, Kohtaro. Tohoku University; Japón
Fil: Cisterna Vergara, Solange. Tohoku University; Japón
Fil: Baillo, Ayelen Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
Fil: Lorenzo Pisarello, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
Fil: Gong, Weichen. Tohoku University; Japón
Fil: Nishiyama, Keita. Tohoku University; Japón
Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; Japón
Fil: Kitazawa, Haruki. Tohoku University; Japón
description Background: Respiratory bacterial infections represent a major health challenge in swineproduction, highlighting the need for novel immunomodulatory strategies that enhancehost resistance. In this study, we investigated whether porcine intestinal lactobacilli couldmodulate the gut–lung axis and improve respiratory innate immunity in a mouse model ofStreptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) wereorally administered to Swiss mice prior to pneumococcal challenge. The resistance tothe infection, the lung damage and the respiratory innate immune response were evaluated. Results: Only strain LAFF998 significantly reduced pulmonary bacterial loads,prevented bacteremia, and attenuated lung injury. This protective effect was associatedwith selective modulation of respiratory immunity, characterized by reduced neutrophilicinflammation, increased lymphocyte recruitment, and enhanced activation of alveolarmacrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-β, IFN-γ, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages fromLAFF998-treated mice exhibited a primed phenotype with heightened cytokine responsesto pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to conferprotection or significantly modulate respiratory immune responses. Conclusions: Thesefindings demonstrate a strict strain-dependent effect among porcine L. salivarius isolatesand identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innateimmunity through the gut–lung axis. This work supports further studies of LAFF998 as animmunobiotic strategy for the prevention of respiratory infections in pigs.
publishDate 2026
dc.date.none.fl_str_mv 2026-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/290132
Fukuyama, Kohtaro; Cisterna Vergara, Solange; Baillo, Ayelen Antonella; Lorenzo Pisarello, Maria Jose; Gong, Weichen; et al.; Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae; Multidisciplinary Digital Publishing Institute; Animals; 16; 5; 3-2026; 1-15
2076-2615
CONICET Digital
CONICET
url http://hdl.handle.net/11336/290132
identifier_str_mv Fukuyama, Kohtaro; Cisterna Vergara, Solange; Baillo, Ayelen Antonella; Lorenzo Pisarello, Maria Jose; Gong, Weichen; et al.; Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae; Multidisciplinary Digital Publishing Institute; Animals; 16; 5; 3-2026; 1-15
2076-2615
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-2615/16/5/825
info:eu-repo/semantics/altIdentifier/doi/10.3390/ani16050825
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.265058

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