Macrophages as drivers of an opportunistic infection
| Autor: | Yara Tasrini, Nazareth Lopez Carranza, Annemarie H. Meijer, David O'Callaghan, Annette C. Vergunst, Margarida C. Gomes, Lili Zhang |
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| Přispěvatelé: | Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institute of Biology, University of Leiden, Universiteit Leiden [Leiden], Vergunst, Annette |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Embryology Burkholderia cenocepacia Neutrophils Opportunistic infection Applied Microbiology [SDV]Life Sciences [q-bio] Pathology and Laboratory Medicine medicine.disease_cause Applied Microbiology and Biotechnology [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity cystic fibrosis White Blood Cells Animal Cells Medicine and Health Sciences lcsh:QH301-705.5 Immune Response Routes of Administration biology intracellular bacteria Fishes Animal Models opportunistic infections Bacterial Pathogens 3. Good health macrophages [SDV] Life Sciences [q-bio] [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Experimental Organism Systems Medical Microbiology Osteichthyes Staphylococcus aureus Vertebrates [SDV.IMM]Life Sciences [q-bio]/Immunology Cellular Types Pathogens Research Article [SDV.IMM] Life Sciences [q-bio]/Immunology Burkholderia Imaging Techniques Immune Cells Immunology Research and Analysis Methods Biochemistry Genetics and Molecular Biology (miscellaneous) Microbiology 03 medical and health sciences Model Organisms Signs and Symptoms Antibiotic resistance Diagnostic Medicine Intravenous Injections Virology Fluorescence Imaging Genetics medicine nosocomial infections Animals Microbial Pathogens Molecular Biology [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity Pharmacology Inflammation Blood Cells Bacteria Pseudomonas aeruginosa Intracellular parasite Embryos Organisms Biology and Life Sciences Cell Biology biology.organism_classification medicine.disease zebrafish Burkholderia cepacia complex 030104 developmental biology lcsh:Biology (General) Parasitology biofilms Developmental Biology |
| Zdroj: | Microbial Cell Microbial Cell, Shared Science Publishers OG, 2017, 4 (10), pp.362-364. ⟨10.15698/mic2017.10.595⟩ MICROBIAL CELL, 4(10), 362-364 MICROBIAL CELL PLoS Pathogens Microbial Cell, Vol 4, Iss 10, Pp 362-364 (2017) |
| ISSN: | 2311-2638 |
| DOI: | 10.15698/mic2017.10.595⟩ |
| Popis: | 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. Author summary Burkholderia cenocepacia is a bacterial pathogen that increases morbidity and mortality in cystic fibrosis patients, but can also cause serious hospital-acquired infections. In this work we demonstrate that macrophages, but not neutrophils, critically contribute to the development of a rapidly fatal inflammatory infection caused by B. cenocepacia. In contrast to findings with other important human pathogens, including Mycobacterium and Salmonella, Bcc bacteria cannot replicate in zebrafish embryos depleted of macrophages, identifying macrophages as a critical site for bacterial replication in vivo. Our study sheds light on the contribution of infected macrophages to infection outcome in an animal model, and contributes a paradigm changing concept of the infection mechanism of this class of bacterial pathogens. |
| Databáze: | OpenAIRE |
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