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

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.

[1]  S. Kurata,et al.  The Ability of Postimmunobiotics from L. rhamnosus CRL1505 to Protect against Respiratory Syncytial Virus and Pneumococcal Super-Infection Is a Strain-Dependent Characteristic , 2022, Microorganisms.

[2]  Xiaoli Zhang,et al.  Host Immune Response to Clinical Hypervirulent Klebsiella pneumoniae Pulmonary Infections via Transcriptome Analysis , 2022, Journal of immunology research.

[3]  S. Kurata,et al.  Respiratory Commensal Bacteria Increase Protection against Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Infection , 2022, Pathogens.

[4]  X. Pan,et al.  Liver Abscess Combined with Endogenous Endophthalmitis Caused by Genotype ST25 Serotype K2 Hypervirulent Klebsiella pneumoniae: A Case Report , 2022, Infection and drug resistance.

[5]  S. Kurata,et al.  Genomic and Immunological Characterization of Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Isolates from Northwest Argentina , 2022, International journal of molecular sciences.

[6]  Lingfei Hu,et al.  Time-Course Transcriptome Analysis of Lungs From Mice Infected With Hypervirulent Klebsiella pneumoniae via Aerosolized Intratracheal Inoculation , 2022, Frontiers in Cellular and Infection Microbiology.

[7]  D. Rosen,et al.  Murine Respiratory Tract Infection with Classical Klebsiella pneumoniae Induces Bronchus-Associated Lymphoid Tissue , 2022, Infection and immunity.

[8]  Yunsong Yu,et al.  Anticolonization of Carbapenem-Resistant Klebsiella pneumoniae by Lactobacillus plantarum LP1812 Through Accumulated Acetic Acid in Mice Intestinal , 2021, Frontiers in Cellular and Infection Microbiology.

[9]  O. Savinova,et al.  Exoproteome Analysis of Antagonistic Interactions between the Probiotic Bacteria Limosilactobacillus reuteri LR1 and Lacticaseibacillus rhamnosus F and Multidrug Resistant Strain of Klebsiella pneumonia , 2021, International journal of molecular sciences.

[10]  H. Kitazawa,et al.  Draft genome sequences of two hypermucoviscous carbapenem-resistant ST25 Klebsiella pneumoniae strains causing respiratory and systemic infections. , 2021, Journal of global antimicrobial resistance.

[11]  A. Prince,et al.  An acquired acyltransferase promotes Klebsiella pneumoniae ST258 respiratory infection , 2020, Cell reports.

[12]  Hideki Takahashi,et al.  Alveolar Macrophages Are Key Players in the Modulation of the Respiratory Antiviral Immunity Induced by Orally Administered Lacticaseibacillus rhamnosus CRL1505 , 2020, Frontiers in Immunology.

[13]  H. Kitazawa,et al.  The Modulation of Mucosal Antiviral Immunity by Immunobiotics: Could They Offer Any Benefit in the SARS-CoV-2 Pandemic? , 2020, Frontiers in Physiology.

[14]  B. Zhu,et al.  Co-infection with respiratory pathogens among COVID-2019 cases , 2020, Virus Research.

[15]  Hideki Takahashi,et al.  Efficient Selection of New Immunobiotic Strains With Antiviral Effects in Local and Distal Mucosal Sites by Using Porcine Intestinal Epitheliocytes , 2020, Frontiers in Immunology.

[16]  M. El-Mokhtar,et al.  Antagonistic Activities of Cell-Free Supernatants of Lactobacilli Against Extended-Spectrum β-Lactamase Producing Klebsiella pneumoniae and Pseudomonas aeruginosa , 2020, Infection and drug resistance.

[17]  Antibiotic resistance threats in the United States, 2019 , 2019 .

[18]  S. Miquel,et al.  Immunomodulatory Effects of Lactobacillus plantarum on Inflammatory Response Induced by Klebsiella pneumoniae , 2019, Infection and Immunity.

[19]  T. Raras,et al.  Anti-Biofilm Activity of Lactic Acid Bacteria Isolated from Kefir Against Multidrug-Resistant Klebsiella pneumoniae , 2019, Journal of Pure and Applied Microbiology.

[20]  G. Gutkind,et al.  Changing Epidemiology of KPC Producing Klebsiella pneumoniae in Argentina: Emergence of Hypermucoviscous ST25 and High Risk Clone ST307. , 2019, Journal of global antimicrobial resistance.

[21]  J. M. Vargas,et al.  Virulence factors and clinical patterns of multiple-clone hypermucoviscous KPC-2 producing K. pneumoniae , 2019, Heliyon.

[22]  T. Russo,et al.  Hypervirulent Klebsiella pneumoniae , 2019, Clinical Microbiology Reviews.

[23]  G. Arlet,et al.  Novel patterns in the molecular epidemiology of KPC-producing Klebsiella pneumoniae in Tucuman, Argentina. , 2019, Journal of global antimicrobial resistance.

[24]  C. Lloyd,et al.  Regulatory cytokine function in the respiratory tract , 2019, Mucosal Immunology.

[25]  A. Prince,et al.  Interleukin-10 Produced by Myeloid-Derived Suppressor Cells Provides Protection to Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 by Enhancing Its Clearance in the Airways , 2019, Infection and Immunity.

[26]  Yi Yan Yang,et al.  Antimicrobial polymers as therapeutics for treatment of multidrug-resistant Klebsiella pneumoniae lung infection. , 2018, Acta biomaterialia.

[27]  A. Suvorov,et al.  Influence of monostrain and multistrain probiotics on immunity, intestinal ultrastructure and microbiota in experimental dysbiosis. , 2018, Beneficial microbes.

[28]  P. Langella,et al.  Opposing effect of Lactobacillus on in vitro Klebsiella pneumoniae in biofilm and in an in vivo intestinal colonisation model. , 2017, Beneficial microbes.

[29]  M. Teixeira,et al.  Control of Klebsiella pneumoniae pulmonary infection and immunomodulation by oral treatment with the commensal probiotic Bifidobacterium longum 5(1A). , 2016, Microbes and infection.

[30]  T. van der Poll,et al.  The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia , 2015, Gut.

[31]  H. Kitazawa,et al.  Modulation of Respiratory TLR3-Anti-Viral Response by Probiotic Microorganisms: Lessons Learned from Lactobacillus rhamnosus CRL1505 , 2014, Front. Immunol..

[32]  H. Kitazawa,et al.  Immunobiotic Lactobacillus rhamnosus improves resistance of infant mice against respiratory syncytial virus infection. , 2013, International immunopharmacology.

[33]  E. Wherry,et al.  Commensal bacteria calibrate the activation threshold of innate antiviral immunity. , 2012, Immunity.

[34]  C. Vay,et al.  Hyperendemic clone of KPC producing Klebsiellapneumoniae ST 258 in Buenos Aires hospitals. , 2012, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[35]  M. Teixeira,et al.  Transient TLR Activation Restores Inflammatory Response and Ability To Control Pulmonary Bacterial Infection in Germfree Mice , 2012, The Journal of Immunology.

[36]  M. Galas,et al.  Clonal dissemination of Klebsiella pneumoniae ST258 harbouring KPC-2 in Argentina. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[37]  A. Iwasaki,et al.  Microbiota regulates immune defense against respiratory tract influenza A virus infection , 2011, Proceedings of the National Academy of Sciences.

[38]  J. Villena,et al.  Immunomodulatory activity of Lactobacillus rhamnosus strains isolated from goat milk: impact on intestinal and respiratory infections. , 2010, International journal of food microbiology.

[39]  J. Shellito,et al.  Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae , 2005, The Journal of experimental medicine.

[40]  T. Standiford,et al.  Defective innate antibacterial host responses during murine Klebsiella pneumoniae bacteremia: tumor necrosis factor (TNF) receptor 1 deficiency versus therapy with anti-TNF-alpha. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.