Hypervirulent <i>Klebsiella pneumoniae</i> Strains Modulate Human Dendritic Cell Functions and Affect T<sub>H</sub>1/T<sub>H</sub>17 Response
Hypervirulent <i>Klebsiella pneumoniae</i> (Hv-Kp) strains have emerged as pathogens causing life-threatening, invasive disease even in immunocompetent hosts. Systemic dissemination usually occurs following perturbations of the gut microbiota and is facilitated by Hv-Kp resistance to pha...
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MDPI AG
2022-02-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/2/384 |
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| author | Sabrina Nicolò Giorgio Mattiuz Alberto Antonelli Fabio Arena Vincenzo Di Pilato Tommaso Giani Ilaria Baccani Ann Maria Clemente Giuseppe Castronovo Michele Tanturli Federico Cozzolino Gian Maria Rossolini Maria Gabriella Torcia |
| author_facet | Sabrina Nicolò Giorgio Mattiuz Alberto Antonelli Fabio Arena Vincenzo Di Pilato Tommaso Giani Ilaria Baccani Ann Maria Clemente Giuseppe Castronovo Michele Tanturli Federico Cozzolino Gian Maria Rossolini Maria Gabriella Torcia |
| author_sort | Sabrina Nicolò |
| collection | DOAJ |
| description | Hypervirulent <i>Klebsiella pneumoniae</i> (Hv-Kp) strains have emerged as pathogens causing life-threatening, invasive disease even in immunocompetent hosts. Systemic dissemination usually occurs following perturbations of the gut microbiota and is facilitated by Hv-Kp resistance to phagocytosis and complement activity. Hv-Kp are usually associated with K1 or K2 capsular types, produce several iron uptake systems (e.g., aerobactin and salmochelin) and are often but not invariably, capsular material hyper-producers (hypermucoviscous phenotype: HMV). Whether Hv-Kp escape the immune response at mucosal site is unknown. In this work, we studied the effects of Hv-Kp on human dendritic cells (DCs), central players of the IL-23/IL-17 and IL-12/IFN-γ axis at mucosal sites, essential for pathogen clearance. Four Hv-Kp and HMV strains were selected and their activity on DC maturation and cytokine production was compared to that of non-virulent Kp strains with classic or HMV phenotypes. While the maturation process was equally induced by all Kp strains, significant differences between virulent and non-virulent strains were found in the expression of genes for cytokines involved in T-cell activation and differentiation. The non-virulent KP04C62 and the classic Kp, KPC157 induced high expression of T<sub>H</sub>1 (IL-12p70 and TNFα) and T<sub>H</sub>17 cytokines (IL-23, IL-1β and IL-6), while Hv-Kp poorly activated these cytokine genes. Moreover, conditioned media from DCs cultured with non-virulent Kp, either classical or hypercapsulated, induced the activation of IL-17 and IFN-γ genes in preactivated CD4<sup>+</sup>-cells suggesting their T<sub>H</sub>17/T<sub>H</sub>1 differentiation. Conditioned media from Hv-Kp poorly activated IL-17 and IFN-γ genes. In summary, our data indicate that Hv-Kp interfere with DC functions and T-cell differentiation and suggest that the escape from the IL-23/IL-17 and IL-12/IFN-γ axes may contribute to pathogen dissemination in immunocompetent hosts. |
| first_indexed | 2024-03-09T21:24:02Z |
| format | Article |
| id | doaj.art-bf692b36b0f9486296393fbb40796fa7 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T21:24:02Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-bf692b36b0f9486296393fbb40796fa72023-11-23T21:15:18ZengMDPI AGMicroorganisms2076-26072022-02-0110238410.3390/microorganisms10020384Hypervirulent <i>Klebsiella pneumoniae</i> Strains Modulate Human Dendritic Cell Functions and Affect T<sub>H</sub>1/T<sub>H</sub>17 ResponseSabrina Nicolò0Giorgio Mattiuz1Alberto Antonelli2Fabio Arena3Vincenzo Di Pilato4Tommaso Giani5Ilaria Baccani6Ann Maria Clemente7Giuseppe Castronovo8Michele Tanturli9Federico Cozzolino10Gian Maria Rossolini11Maria Gabriella Torcia12Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyClinical Microbiology and Virology Unit, Careggi University Hospital, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyHypervirulent <i>Klebsiella pneumoniae</i> (Hv-Kp) strains have emerged as pathogens causing life-threatening, invasive disease even in immunocompetent hosts. Systemic dissemination usually occurs following perturbations of the gut microbiota and is facilitated by Hv-Kp resistance to phagocytosis and complement activity. Hv-Kp are usually associated with K1 or K2 capsular types, produce several iron uptake systems (e.g., aerobactin and salmochelin) and are often but not invariably, capsular material hyper-producers (hypermucoviscous phenotype: HMV). Whether Hv-Kp escape the immune response at mucosal site is unknown. In this work, we studied the effects of Hv-Kp on human dendritic cells (DCs), central players of the IL-23/IL-17 and IL-12/IFN-γ axis at mucosal sites, essential for pathogen clearance. Four Hv-Kp and HMV strains were selected and their activity on DC maturation and cytokine production was compared to that of non-virulent Kp strains with classic or HMV phenotypes. While the maturation process was equally induced by all Kp strains, significant differences between virulent and non-virulent strains were found in the expression of genes for cytokines involved in T-cell activation and differentiation. The non-virulent KP04C62 and the classic Kp, KPC157 induced high expression of T<sub>H</sub>1 (IL-12p70 and TNFα) and T<sub>H</sub>17 cytokines (IL-23, IL-1β and IL-6), while Hv-Kp poorly activated these cytokine genes. Moreover, conditioned media from DCs cultured with non-virulent Kp, either classical or hypercapsulated, induced the activation of IL-17 and IFN-γ genes in preactivated CD4<sup>+</sup>-cells suggesting their T<sub>H</sub>17/T<sub>H</sub>1 differentiation. Conditioned media from Hv-Kp poorly activated IL-17 and IFN-γ genes. In summary, our data indicate that Hv-Kp interfere with DC functions and T-cell differentiation and suggest that the escape from the IL-23/IL-17 and IL-12/IFN-γ axes may contribute to pathogen dissemination in immunocompetent hosts.https://www.mdpi.com/2076-2607/10/2/384hypervirulenthypermucoviscous <i>K. pneumoniae</i>dendritic cells (DCs)T<sub>H</sub> differentiationinflammatory cytokinesimmune response |
| spellingShingle | Sabrina Nicolò Giorgio Mattiuz Alberto Antonelli Fabio Arena Vincenzo Di Pilato Tommaso Giani Ilaria Baccani Ann Maria Clemente Giuseppe Castronovo Michele Tanturli Federico Cozzolino Gian Maria Rossolini Maria Gabriella Torcia Hypervirulent <i>Klebsiella pneumoniae</i> Strains Modulate Human Dendritic Cell Functions and Affect T<sub>H</sub>1/T<sub>H</sub>17 Response Microorganisms hypervirulent hypermucoviscous <i>K. pneumoniae</i> dendritic cells (DCs) T<sub>H</sub> differentiation inflammatory cytokines immune response |
| title | Hypervirulent <i>Klebsiella pneumoniae</i> Strains Modulate Human Dendritic Cell Functions and Affect T<sub>H</sub>1/T<sub>H</sub>17 Response |
| title_full | Hypervirulent <i>Klebsiella pneumoniae</i> Strains Modulate Human Dendritic Cell Functions and Affect T<sub>H</sub>1/T<sub>H</sub>17 Response |
| title_fullStr | Hypervirulent <i>Klebsiella pneumoniae</i> Strains Modulate Human Dendritic Cell Functions and Affect T<sub>H</sub>1/T<sub>H</sub>17 Response |
| title_full_unstemmed | Hypervirulent <i>Klebsiella pneumoniae</i> Strains Modulate Human Dendritic Cell Functions and Affect T<sub>H</sub>1/T<sub>H</sub>17 Response |
| title_short | Hypervirulent <i>Klebsiella pneumoniae</i> Strains Modulate Human Dendritic Cell Functions and Affect T<sub>H</sub>1/T<sub>H</sub>17 Response |
| title_sort | hypervirulent i klebsiella pneumoniae i strains modulate human dendritic cell functions and affect t sub h sub 1 t sub h sub 17 response |
| topic | hypervirulent hypermucoviscous <i>K. pneumoniae</i> dendritic cells (DCs) T<sub>H</sub> differentiation inflammatory cytokines immune response |
| url | https://www.mdpi.com/2076-2607/10/2/384 |
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