Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae
Klebsiella pneumoniae is the causative agent of a wide range of antibiotic-resistant infections, including nosocomial pneumonia and neonatal sepsis. We investigate here the mechanisms underlying innate immune recognition of this pathogen by focusing on the role of endosomal Toll-like receptors (TLRs...
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| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538425/full |
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| author | Giuseppe Valerio De Gaetano Agata Famà Germana Lentini Francesco Coppolino Mario Venza Isabella Venza Pasqualina Laganà Alessia Berbiglia Federica Grasso Luigi Fiore Giuseppe Teti Concetta Beninati Concetta Beninati |
| author_facet | Giuseppe Valerio De Gaetano Agata Famà Germana Lentini Francesco Coppolino Mario Venza Isabella Venza Pasqualina Laganà Alessia Berbiglia Federica Grasso Luigi Fiore Giuseppe Teti Concetta Beninati Concetta Beninati |
| author_sort | Giuseppe Valerio De Gaetano |
| collection | DOAJ |
| description | Klebsiella pneumoniae is the causative agent of a wide range of antibiotic-resistant infections, including nosocomial pneumonia and neonatal sepsis. We investigate here the mechanisms underlying innate immune recognition of this pathogen by focusing on the role of endosomal Toll-like receptors (TLRs), which sense prokaryotic nucleic acids, in comparison with TLR4, which recognizes the cell-wall lipopolysaccharide component. Lack of functional endosomal TLRs made mice more susceptible to pulmonary infection by K. pneumoniae, in association with reduced production of proinflammatory and chemotactic cytokines and reduced neutrophil recruitment to the lung. This phenotype was as severe as that of TLR4-deficient mice and only moderately milder than that of mice lacking the TLR adaptor MyD88. Notably, macrophages lacking at the same time TLR7, 9 and 13 were more defective than those lacking only TLR9 in their ability to produce proinflammatory cytokines, suggesting a role for the RNA sensing TLR7 and 13 receptors in K. pneumoniae recognition. Collectively, our results unveil the presence of an integrated system of DNA and RNA sensing TLRs that cooperates with TLR4 in immune detection and clearance of K. pneumoniae. These data may be useful to devise alternative therapeutic approaches aimed at stimulating responses against antibiotic-resistant K. pneumoniae strains. |
| format | Article |
| id | doaj-art-06d5dc1ada504d6c8a2854d1f7a3cb8f |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-06d5dc1ada504d6c8a2854d1f7a3cb8f2025-08-20T01:55:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15384251538425Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniaeGiuseppe Valerio De Gaetano0Agata Famà1Germana Lentini2Francesco Coppolino3Mario Venza4Isabella Venza5Pasqualina Laganà6Alessia Berbiglia7Federica Grasso8Luigi Fiore9Giuseppe Teti10Concetta Beninati11Concetta Beninati12Department of Human Pathology “Gaetano Barresi”, University of Messina, Messina, ItalyDepartment of Human Pathology “Gaetano Barresi”, University of Messina, Messina, ItalyDepartment of Human Pathology “Gaetano Barresi”, University of Messina, Messina, ItalyDepartment of Human Pathology “Gaetano Barresi”, University of Messina, Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphological and Functional Images, University of Messina, Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphological and Functional Images, University of Messina, Messina, ItalyDepartment of Human Pathology “Gaetano Barresi”, University of Messina, Messina, ItalyDepartment of Human Pathology “Gaetano Barresi”, University of Messina, Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphological and Functional Images, University of Messina, Messina, ItalyScylla Biotech Srl, Messina, ItalyDepartment of Human Pathology “Gaetano Barresi”, University of Messina, Messina, ItalyScylla Biotech Srl, Messina, ItalyKlebsiella pneumoniae is the causative agent of a wide range of antibiotic-resistant infections, including nosocomial pneumonia and neonatal sepsis. We investigate here the mechanisms underlying innate immune recognition of this pathogen by focusing on the role of endosomal Toll-like receptors (TLRs), which sense prokaryotic nucleic acids, in comparison with TLR4, which recognizes the cell-wall lipopolysaccharide component. Lack of functional endosomal TLRs made mice more susceptible to pulmonary infection by K. pneumoniae, in association with reduced production of proinflammatory and chemotactic cytokines and reduced neutrophil recruitment to the lung. This phenotype was as severe as that of TLR4-deficient mice and only moderately milder than that of mice lacking the TLR adaptor MyD88. Notably, macrophages lacking at the same time TLR7, 9 and 13 were more defective than those lacking only TLR9 in their ability to produce proinflammatory cytokines, suggesting a role for the RNA sensing TLR7 and 13 receptors in K. pneumoniae recognition. Collectively, our results unveil the presence of an integrated system of DNA and RNA sensing TLRs that cooperates with TLR4 in immune detection and clearance of K. pneumoniae. These data may be useful to devise alternative therapeutic approaches aimed at stimulating responses against antibiotic-resistant K. pneumoniae strains.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538425/fullgram negative bacteriapneumonitispattern recognition receptorsneutrophilscytokinesbacterial RNA |
| spellingShingle | Giuseppe Valerio De Gaetano Agata Famà Germana Lentini Francesco Coppolino Mario Venza Isabella Venza Pasqualina Laganà Alessia Berbiglia Federica Grasso Luigi Fiore Giuseppe Teti Concetta Beninati Concetta Beninati Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae Frontiers in Immunology gram negative bacteria pneumonitis pattern recognition receptors neutrophils cytokines bacterial RNA |
| title | Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae |
| title_full | Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae |
| title_fullStr | Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae |
| title_full_unstemmed | Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae |
| title_short | Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae |
| title_sort | role of endosomal toll like receptors in immune sensing of klebsiella pneumoniae |
| topic | gram negative bacteria pneumonitis pattern recognition receptors neutrophils cytokines bacterial RNA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538425/full |
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