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
-
- Animals
- Burkholderia Infections/immunology
- Burkholderia cenocepacia/isolation & purification*
- Burkholderia cepacia complex/immunology
- Cross Infection/microbiology*
- Cystic Fibrosis/complications
- Humans
- Inflammation/microbiology*
- Lung/microbiology
- Macrophages/microbiology*
- Neutrophils/immunology
- Neutrophils/microbiology*
- Phagocytosis/immunology
- Pseudomonas aeruginosa/physiology
- Respiratory Tract Infections/microbiology
- PubMed
- 28651010 Full text @ PLoS Pathog.
Citation
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. (2017) Macrophages, but not neutrophils, are critical for proliferation of Burkholderia cenocepacia and ensuing host-damaging inflammation. PLoS pathogens. 13:e1006437.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping