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

Abstract

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.