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

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...

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Bibliographic Details
Published in:PLoS pathogens 2017-06, Vol.13 (6), p.e1006437-e1006437
Main Authors: Mesureur, Jennifer, Feliciano, Joana R, Wagner, Nelly, Gomes, Margarida C, Zhang, Lili, Blanco-Gonzalez, Monica, van der Vaart, Michiel, O'Callaghan, David, Meijer, Annemarie H, Vergunst, Annette C
Format: Article
Language:English
Subjects:
Animals
Antimicrobial agents
Bacteria
Biology
Biology and Life Sciences
Burkholderia
Burkholderia cenocepacia - isolation & purification
Burkholderia cepacia complex - immunology
Burkholderia Infections - immunology
Chronic infection
Cross Infection - microbiology
Cystic fibrosis
Cystic Fibrosis - complications
Damage
Funding
Higher education
Human health and pathology
Humans
Immunology
In vitro methods and tests
Infectious diseases
Inflammation
Inflammation - microbiology
Inflammatory response
Innate immunity
Interleukin 1
Intracellular
Larvae
Leukocytes (neutrophilic)
Life Sciences
Lung - microbiology
Lung diseases
Lungs
Macrophages
Macrophages - microbiology
Mammalian cells
Medicine and Health Sciences
Methods
Multiplication
NAD(P)H oxidase
Neutrophils
Neutrophils - immunology
Neutrophils - microbiology
Nosocomial infection
Nosocomial infections
Opportunist infection
Oxidase
Pathogens
Patients
Phagocytes
Phagocytosis
Phagocytosis - immunology
Pseudomonas aeruginosa
Pseudomonas aeruginosa - physiology
Recurrent infection
Research and Analysis Methods
Respiratory Tract Infections - microbiology
Roles
Septicemia
Signaling
Zebrafish
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Summary: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 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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1006437