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Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia.
J Innate Immun 2016; 8(3):258-68JI

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.

Authors+Show Affiliations

Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26894590

Citation

García-Laorden, M Isabel, et al. "Granzymes a and B Regulate the Local Inflammatory Response During Klebsiella Pneumoniae Pneumonia." Journal of Innate Immunity, vol. 8, no. 3, 2016, pp. 258-68.
García-Laorden MI, Stroo I, Blok DC, et al. Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia. J Innate Immun. 2016;8(3):258-68.
García-Laorden, M. I., Stroo, I., Blok, D. C., Florquin, S., Medema, J. P., de Vos, A. F., & van der Poll, T. (2016). Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia. Journal of Innate Immunity, 8(3), pp. 258-68. doi:10.1159/000443401.
García-Laorden MI, et al. Granzymes a and B Regulate the Local Inflammatory Response During Klebsiella Pneumoniae Pneumonia. J Innate Immun. 2016;8(3):258-68. PubMed PMID: 26894590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia. AU - García-Laorden,M Isabel, AU - Stroo,Ingrid, AU - Blok,Dana C, AU - Florquin,Sandrine, AU - Medema,Jan Paul, AU - de Vos,Alex F, AU - van der Poll,Tom, Y1 - 2016/02/20/ PY - 2015/10/22/received PY - 2015/12/16/accepted PY - 2016/2/20/entrez PY - 2016/2/20/pubmed PY - 2017/9/25/medline SP - 258 EP - 68 JF - Journal of innate immunity JO - J Innate Immun VL - 8 IS - 3 N2 - 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. SN - 1662-8128 UR - https://www.unboundmedicine.com/medline/citation/26894590/Granzymes_A_and_B_Regulate_the_Local_Inflammatory_Response_during_Klebsiella_pneumoniae_Pneumonia_ L2 - https://www.karger.com?DOI=10.1159/000443401 DB - PRIME DP - Unbound Medicine ER -