PUBLICATION

Macrophages, but not neutrophils, are critical for proliferation of Burkholderia cenocepacia and ensuing host-damaging inflammation

Authors
Mesureur, J., Feliciano, J.R., Wagner, N., Gomes, M.C., Zhang, L., Blanco-Gonzalez, M., van der Vaart, M., O'Callaghan, D., Meijer, A.H., Vergunst, A.C.
ID
ZDB-PUB-170627-2
Date
2017
Source
PLoS pathogens   13: e1006437 (Journal)
Registered Authors
Meijer, Annemarie H., Mesureur, Jennifer, van der Vaart, Michiel, Vergunst, Annette, Zhang, Lili
Keywords
Embryos, Macrophages, Burkholderia cenocepacia, Neutrophils, Zebrafish, Fluorescence imaging, Intravenous injections, Inflammation
MeSH Terms
  • Burkholderia cepacia complex/immunology
  • Lung/microbiology
  • Inflammation/microbiology*
  • Respiratory Tract Infections/microbiology
  • Macrophages/microbiology*
  • Neutrophils/immunology
  • Neutrophils/microbiology*
  • Cystic Fibrosis/complications
  • Cross Infection/microbiology*
  • Burkholderia Infections/immunology
  • Burkholderia cenocepacia/isolation & purification*
  • Pseudomonas aeruginosa/physiology
  • Humans
  • Animals
  • Phagocytosis/immunology
(all 15)
PubMed
28651010 Full text @ PLoS Pathog.
Abstract
Bacteria of the Burkholderia cepacia complex (Bcc) can cause devastating pulmonary infections in cystic fibrosis (CF) patients, yet the precise mechanisms underlying inflammation, recurrent exacerbations and transition from chronic stages to acute infection and septicemia are not known. Bcc bacteria are generally believed to have a predominant extracellular biofilm life style in infected CF lungs, similar to Pseudomonas aeruginosa, but this has been challenged by clinical observations which show Bcc bacteria predominantly in alveolar macrophages. More recently, Bcc bacteria have emerged in nosocomial infections of patients hospitalized for reasons unrelated to CF. Research has abundantly shown that Bcc bacteria can survive and replicate in mammalian cells in vitro, yet the importance of an intracellular life style during infection in humans is unknown. Here we studied the contribution of innate immune cell types to fatal pro-inflammatory infection caused by B. cenocepacia using zebrafish larvae. In strong contrast to the usual protective role for macrophages against microbes, our results show that these phagocytes significantly worsen disease outcome. We provide new insight that macrophages are critical for multiplication of B. cenocepacia in the host and for development of a fatal, pro-inflammatory response that partially depends on Il1-signalling. In contrast, neutrophils did not significantly contribute to disease outcome. In subcutaneous infections that are dominated by neutrophil-driven phagocytosis, the absence of a functional NADPH oxidase complex resulted in a small but measurably higher increase in bacterial growth suggesting the oxidative burst helps limit bacterial multiplication; however, neutrophils were unable to clear the bacteria. We suggest that paradigm-changing approaches are needed for development of novel antimicrobials to efficiently disarm intracellular bacteria of this group of highly persistent, opportunistic pathogens.
Errata / Notes
This article is corrected by ZDB-PUB-220906-91 .
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1
    Point Mutation
    gl24TgTransgenic Insertion
      hu3568
        Point Mutation
        i114TgTransgenic Insertion
          i149TgTransgenic Insertion
            i186TgTransgenic Insertion
              s1999tTgTransgenic Insertion
                sh267TgTransgenic Insertion
                  ump2TgTransgenic Insertion
                    ump3TgTransgenic Insertion
                      1 - 10 of 10
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                      Human Disease / Model
                      1 - 1 of 1
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                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      csf3rMO3-csf3rMRPHLNO
                      cybbMO2-cybbMRPHLNO
                      il1bMO1-il1bMRPHLNO
                      myd88MO1-myd88MRPHLNO
                      myd88MO2-myd88MRPHLNO
                      spi1bMO2-spi1bMRPHLNO
                      spi1bMO3-spi1bMRPHLNO
                      1 - 7 of 7
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                      Fish
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab2-lcp1polyclonalRabbit
                      1 - 1 of 1
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                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      GFPEFGGFP
                      KaedeEFGKaede
                      mCherryEFGmCherry
                      NTREFGNTR
                      1 - 6 of 6
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                      Mapping
                      No data available