# Combined Lactiplantibacillus plantarum CRL1506 and MPL16 Nasal Priming More Effectively Modulates Respiratory Antiviral Innate Immunity than Single Strains

## TL;DR

Combining two Lactiplantibacillus plantarum strains improves antiviral immunity in mice more than using either strain alone.

## Contribution

The study demonstrates that a combination of two Lactiplantibacillus strains modulates antiviral immunity more effectively than single strains in respiratory models.

## Key findings

- The CRL1506 + MPL16 combination reduced RSV replication and lung injury better than single strains in mice.
- CRL1506 induced higher IFN-λ production in respiratory epithelial cells compared to MPL16.
- The combination's effectiveness likely comes from complementary actions on macrophages and epithelial cells.

## Abstract

This study evaluated whether the combined Lactiplantibacillus plantarum CRL1506 and MPL16 nasal priming more effectively modulated the Toll-like receptor (TLR)-3- and respiratory syncytial virus (RSV)-mediated respiratory immune responses in mice than single strains. The interaction of single and combined strains with porcine alveolar macrophages (AMs) and porcine respiratory epithelial cells (PBE cells) in the context of TLR3 activation and porcine reproductive and respiratory syndrome virus (PRRSV) was also evaluated. The in vivo studies in mice revealed that the CRL1506 + MPL16 combination was more effective than the individual strains at reducing RSV replication, protecting the lung from TLR3-mediated inflammatory injury and modulating innate antiviral responses, particularly in AMs. In vitro, lactobacilli treatment also increased the resistance of porcine AMs to PRRSV infection. Notably, the CRL1506 + MPL16 combination was not more effective than the single strains in modulating AMs antiviral immunity. Complementary assays in PBE cells revealed that L. plantarum CRL1506 induced higher production of IFN-λ than the MPL16 strain in response to TLR3 activation. Thus, the superior in vivo protection against RSV seen with the L. plantarum CRL1506–MPL16 combination likely reflects complementary actions of lactobacilli: MPL16 would efficiently modulate AMs, whereas CRL1506 would be more effective to target respiratory epithelial cells driving greater IFN-λ production that further boosts AM antiviral activity. The results from the animal models of this work furnish the scientific basis for proposing future human trials to assess the efficacy of the CRL1506 + MPL16 combination in improving respiratory antiviral immunity.