Hypervirulent Klebsiella pneumoniae (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-gamma 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(H)1 (IL-12p70 and TNF alpha) and T(H)17 cytokines (IL-23, IL-1 beta 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-gamma genes in preactivated CD4(+)-cells suggesting their T(H)17/T(H)1 differentiation. Conditioned media from Hv-Kp poorly activated IL-17 and IFN-gamma 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-gamma axes may contribute to pathogen dissemination in immunocompetent hosts.

Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect TH1/TH17 Response / Nicolò, Sabrina; Mattiuz, Giorgio; Antonelli, Alberto; Arena, Fabio; Di Pilato, Vincenzo; Giani, Tommaso; Baccani, Ilaria; Clemente, Ann Maria; Castronovo, Giuseppe; Tanturli, Michele; Cozzolino, Federico; Rossolini, Gian Maria; Torcia, Maria Gabriella. - In: MICROORGANISMS. - ISSN 2076-2607. - ELETTRONICO. - 10:(2022), pp. 384-384. [10.3390/microorganisms10020384]

Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect TH1/TH17 Response

Mattiuz, Giorgio;Antonelli, Alberto;Arena, Fabio;Di Pilato, Vincenzo;Giani, Tommaso;Baccani, Ilaria;Clemente, Ann Maria;Castronovo, Giuseppe;Tanturli, Michele;Cozzolino, Federico;Rossolini, Gian Maria;Torcia, Maria Gabriella
2022

Abstract

Hypervirulent Klebsiella pneumoniae (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-gamma 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(H)1 (IL-12p70 and TNF alpha) and T(H)17 cytokines (IL-23, IL-1 beta 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-gamma genes in preactivated CD4(+)-cells suggesting their T(H)17/T(H)1 differentiation. Conditioned media from Hv-Kp poorly activated IL-17 and IFN-gamma 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-gamma axes may contribute to pathogen dissemination in immunocompetent hosts.
2022
10
384
384
Nicolò, Sabrina; Mattiuz, Giorgio; Antonelli, Alberto; Arena, Fabio; Di Pilato, Vincenzo; Giani, Tommaso; Baccani, Ilaria; Clemente, Ann Maria; Castronovo, Giuseppe; Tanturli, Michele; Cozzolino, Federico; Rossolini, Gian Maria; Torcia, Maria Gabriella
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1285097
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