Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media

Short, Kirsty R., von Kochritz-Blickwede, Maren, Langereis, Jeroen D., Chew, Keng Yih, Job, Emma R., Armitage, Charles W., Hatcher, Brandon, Fujihashi, Kohtaro, Reading, Patrick C., Hermans, Peter W., Wijburg, Odilia L., & Diavatopoulos, Dimitri A. (2014) Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media. Infection and Immunity, 82(1), pp. 364-370.

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Abstract

Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus). We and others have demonstrated that coinfection with IAV facilitates the replication of pneumococci in the middle ear. Specifically, we used a mouse model of OM to show that IAV facilitates the outgrowth of S. pneumoniae in the middle ear by inducing middle ear inflammation. Here, we seek to understand how the host inflammatory response facilitates bacterial outgrowth in the middle ear. Using B cell-deficient infant mice, we show that antibodies play a crucial role in facilitating pneumococcal replication. We subsequently show that this is due to antibody-dependent neutrophil extracellular trap (NET) formation in the middle ear, which, instead of clearing the infection, allows the bacteria to replicate. We further demonstrate the importance of these NETs as a potential therapeutic target through the transtympanic administration of a DNase, which effectively reduces the bacterial load in the middle ear. Taken together, these data provide novel insight into how pneumococci are able to replicate in the middle ear cavity and induce disease.

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16 citations in Scopus
17 citations in Web of Science®
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ID Code: 70902
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 6 months
Additional URLs:
DOI: 10.1128/IAI.01104-13
ISSN: 0019-9567
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > IMMUNOLOGY (110700) > Cellular Immunology (110704)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > IMMUNOLOGY (110700) > Humoural Immunology and Immunochemistry (110705)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL MICROBIOLOGY (110800) > Medical Bacteriology (110801)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL MICROBIOLOGY (110800) > Medical Virology (110804)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 American Society for Microbiology
Deposited On: 02 May 2014 01:52
Last Modified: 22 Jun 2017 09:05

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