Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia.

Abstract:

:Klebsiella pneumoniae is a common cause of hospital-acquired pneumonia. Granzymes (gzms), mainly found in cytotoxic lymphocytes, have been implicated as mediators of infection and inflammation. We here sought to investigate the role of gzmA and gzmB in the host response to K. pneumoniae-induced airway infection and sepsis. For this purpose, pneumonia was induced in wild-type (WT) and gzmA-deficient (gzmA-/-), gzmB-/- and gzmAxB-/- mice by intranasal infection with K. pneumoniae. In WT mice, gzmA and gzmB were mainly expressed by natural killer cells. Pneumonia was associated with reduced intracellular gzmA and increased intracellular gzmB levels. Gzm deficiency had little impact on antibacterial defence: gzmA-/- and gzmAxB-/- mice transiently showed modestly higher bacterial loads in the lungs but not in distant organs. GzmB-/- and, to a larger extent, gzmAxB-/- mice displayed transiently increased lung inflammation, reflected in the semi-quantitative histology scores and levels of pro-inflammatory cytokines and chemokines. Most differences between gzm-deficient and WT mice had disappeared during late-stage pneumonia. Gzm deficiency did not impact on distant organ injury or survival. These results suggest that gzmA and gzmB partly regulate local inflammation during early pneumonia but eventually play an insignificant role during pneumosepsis by the common human pathogen K. pneumoniae.

journal_name

J Innate Immun

authors

García-Laorden MI,Stroo I,Blok DC,Florquin S,Medema JP,de Vos AF,van der Poll T

doi

10.1159/000443401

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

258-68

issue

3

eissn

1662-811X

issn

1662-8128

pii

000443401

journal_volume

8

pub_type

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