Respiratory viral infections remain a major health concern, highlighting the need for strategies that enhance host antiviral defenses. Lacticaseibacillus rhamnosus CRL1505 has demonstrated beneficial immunomodulatory effects in the respiratory tract; however, its direct effects on distinct respiratory cell populations remain incompletely characterized. Here, we evaluated the capacity of live and HK 1505 to modulate antiviral immunity in porcine bronchial epithelial (PBE) cells challenged with SIV and porcine alveolar macrophage (PAM) cells infected with PRRSV. Pretreatment with either live or HK 1505 significantly reduced infectious SIV titers in PBE cells and decreased PRRSV ORF5 expression and viral antigen detection in PAM cells, accompanied by enhanced expression of interferons and antiviral factors in both models. CRL1505 also differentially modulated inflammatory responses according to the cell type. In PAM cells, both treatments enhanced proinflammatory and regulatory cytokines, whereas in PBE cells they selectively increased IL-1β and IL-6 while reducing TNF-α, IL-8, and MCP-1. Negative regulators of innate immune signaling were also differentially modulated in both cell types. Importantly, HK 1505 retained significant antiviral and immunomodulatory activities, inducing responses that were generally similar to those observed with the viable preparation under the experimental conditions evaluated. These findings demonstrate that L. rhamnosus CRL1505 enhances antiviral responses in two distinct respiratory cell models, with differences in immunomodulatory profiles that may reflect the combined influence of cellular and viral contexts.

Lactiplantibacillus plantarum strains can protect against intestinal pathogens through direct antagonism and modulation of host immunity, although the bacterial components linking these activities remain poorly understood. Here, we investigated the contribution of surface-associated components to the interaction of L. plantarum with enterohemorrhagic Escherichia coli (EHEC) and intestinal macrophages. L. plantarum CRL681 (Lp681), CRL1506 (Lp1506), and an Lp1506 ΔdltD mutant defective in lipoteichoic acid D-alanylation were compared for aggregation, interaction with EHEC, and antagonistic activity. Lp681 exhibited the highest autoaggregation and coaggregation capacities and the strongest inhibition of EHEC, whereas Lp1506 ΔdltD showed reduced aggregation and no detectable antagonistic activity in coculture. Electron microscopy revealed close associations between Lp681 or Lp1506 and EHEC, accompanied by alterations in pathogen cell-envelope integrity. Removal of the LiCl-extractable surface fraction partially reduced Lp681-mediated inhibition, while the corresponding extracted fraction, enriched in surface-associated proteins, retained direct anti-EHEC activity. In intestinal macrophages challenged with enterotoxigenic E. coli (ETEC), viable Lp681 and LiCl-treated cells induced largely similar cytokine/chemokine gene-expression profiles, whereas the LiCl-extractable fraction retained independent immunomodulatory activity. The pre-exposure of EHEC to Lp681 surface proteins altered its subsequent interaction with macrophages, reducing TNF-α and MCP-1 expression while increasing IL-10 and IL-1β. These findings identify the Lp681 surface as a functional interface connecting pathogen antagonism and host immune modulation and suggest that surface-associated proteins can influence host responses both directly and indirectly through their interaction with the pathogen.

Background: Respiratory bacterial infections represent a major health challenge in swine production, highlighting the need for novel immunomodulatory strategies that enhance host resistance. In this study, we investigated whether porcine intestinal lactobacilli could modulate the gut–lung axis and improve respiratory innate immunity in a mouse model of Streptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) were orally administered to Swiss mice prior to pneumococcal challenge. The resistance to the 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 associated with selective modulation of respiratory immunity, characterized by reduced neutrophilic inflammation, increased lymphocyte recruitment, and enhanced activation of alveolar macrophages 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 from LAFF998-treated mice exhibited a primed phenotype with heightened cytokine responses to pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to confer protection or significantly modulate respiratory immune responses. Conclusions: These findings demonstrate a strict strain-dependent effect among porcine L. salivarius isolates and identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innate immunity through the gut–lung axis. This work supports further studies of LAFF998 as an immunobiotic strategy for the prevention of respiratory infections in pigs.