The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia
| Autor: | Friedrich Koch-Nolte, Carrie A. Cowardin, Anna Marei Eichhoff, Carsten Schwan, Mahmoud M. Saleh, Erica L. Buonomo, Stacey L. Burgess, William A. Petri, Sarah A. Kuehne, Nigel P. Minton, Dena Lyras, Klaus Aktories, Madeline G. Wilson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Colon Virulence Factors 030106 microbiology Immunology Virulence Clostridium difficile toxin A Biology medicine.disease_cause Applied Microbiology and Biotechnology Microbiology Ribotyping Article 03 medical and health sciences Mice Bacterial Proteins Genetics medicine Animals Pathogen ADP Ribose Transferases Pore-forming toxin Innate immune system Toxin Clostridioides difficile Cell Biology Clostridium difficile 3. Good health Eosinophils TLR2 Disease Models Animal 030104 developmental biology Clostridium Infections |
| Zdroj: | Nature microbiology |
| ISSN: | 2058-5276 |
| Popis: | Clostridium difficile is the most common hospital acquired pathogen in the USA, and infection is, in many cases, fatal. Toxins A and B are its major virulence factors, but expression of a third toxin, known as C. difficile transferase (CDT), is increasingly common. An adenosine diphosphate (ADP)-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. Here, we show that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a Toll-like receptor 2 (TLR2)-dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, we show that restoration of TLR2-deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressing C. difficile and demonstrate a mechanism by which this binary toxin subverts the host immune response. Clostridium difficile CDT toxin suppresses protective host eosinophilic responses through TLR2 signalling to induce inflammation. |
| Databáze: | OpenAIRE |
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