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

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

doi:10.3390/microorganisms10020384

Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect T_H1/T_H17 Response

Microorganisms. 2022 Feb 7;10(2):384. doi: 10.3390/microorganisms10020384.

Authors

Sabrina Nicolò¹, Giorgio Mattiuz¹, Alberto Antonelli^{1

2}, Fabio Arena^{3

4}, Vincenzo Di Pilato^{2

5}, Tommaso Giani^{1

2}, Ilaria Baccani^{1

2}, Ann Maria Clemente¹, Giuseppe Castronovo⁶, Michele Tanturli⁶, Federico Cozzolino⁶, Gian Maria Rossolini^{1

2}, Maria Gabriella Torcia¹

Affiliations

¹ Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
² Clinical Microbiology and Virology Unit, Careggi University Hospital, 50134 Florence, Italy.
³ Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.
⁴ IRCCS Fondazione Don Carlo Gnocchi ONLUS, 50143 Florence, Italy.
⁵ Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, 16132 Genoa, Italy.
⁶ Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139 Florence, Italy.

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-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_H1 (IL-12p70 and TNFα) and T_H17 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⁺-cells suggesting their T_H17/T_H1 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.

Keywords: TH differentiation; dendritic cells (DCs); hypermucoviscous K. pneumoniae; hypervirulent; immune response; inflammatory cytokines.

Grants and funding

2014.0740 and 2016.0961/Ente Cassa di Risparmio di Firenze