Oral Administration of Lacticaseibacillus rhamnosus CRL1505 Modulates Lung Innate Immune Response against Klebsiella pneumoniae ST25

Abstract

Orally administered Lacticaseibacillus rhamnosus CRL1505 enhances respiratory immunity, providing protection against respiratory viruses and Streptococcus pneumoniae. However, the capacity of the CRL1505 strain to improve respiratory immunity against Gram-negative bacterial infections has not been evaluated before. The aim of this work was to evaluate whether the Lcb. rhamnosus CRL1505 was able to beneficially regulate the respiratory innate immune response and enhance the resistance to hypermucoviscous KPC-2-producing Klebsiella pneumoniae of the sequence type 25 (ST25). BALB/c mice were treated with the CRL1505 strain via the oral route and then nasally challenged with K. pneumoniae ST25 strains LABACER 01 or LABACER 27. Bacterial cell counts, lung injuries and the respiratory and systemic innate immune responses were evaluated after the bacterial infection. The results showed that K. pneumoniae ST25 strains increased the levels of TNF-α, IL-1β, IL-6, IFN-γ, IL-17, KC and MPC-1 in the respiratory tract and blood, as well as the numbers of BAL neutrophils and macrophages. Mice treated with Lcb. rhamnosus CRL1505 had significantly lower K. pneumoniae counts in their lungs, as well as reduced levels of inflammatory cells, cytokines and chemokines in the respiratory tract and blood when compared to infected controls. Furthermore, higher levels of the regulatory cytokines IL-10 and IL-27 were found in the respiratory tract and blood of CRL1505-treated mice than controls. These results suggest that the ability of Lcb. rhamnosus CRL1505 to help with the control of detrimental inflammation in lungs during K. pneumoniae infection would be a key feature to improve the resistance to this pathogen. Although further mechanistic studies are necessary, Lcb. rhamnosus CRL1505 can be proposed as a candidate to improve patients’ protection against hypermucoviscous KPC-2-producing strains belonging to the ST25, which is endemic in the hospitals of our region.

Investigation on the Efficacy of Two Food Supplements Containing a Fixed Combination of Selected Probiotics and β-Glucans or Elderberry Extract for the Immune System: Modulation on Cytokines Expression in Human THP-1 and PBMC

“…Samples were tested at two different timings, 6 and 24 h, short and long exposure times that simulate a short term and chronic intake and, more important, that cover the whole curve of maximum release of the most part of cytokines as previously verified by our group in different cell lines [12][13][14][15][16][17][18][19][20] and as reported in [22] for THP-1 and [23,24] for PBMC.…”

“…lactis Bl-04 ® , isolated from human intestine) with a yeast derivative (1,3-1,6-β-glucans from Saccharomices cerevisiae); the formulation for children is an association between Lactobacillus rhamnosus CRL1505 (isolated from goat milk) and elderberry extract. The two formulations combine specific probiotic strains, genetically characterized and pre-clinically and clinically tested for immune regulation [13,14], associated with botanical functional ingredients also claimed for their activity on immune system [15]; innovation and rationale of the formulations are witnessed by the release of a patent for their industrial invention [16].…”