Impact of Microbiota on Resistance to Ocular Pseudomonas aeruginosa-Induced Keratitis

Autor: Thomas Vorup-Jensen, Mihaela Gadjeva, Stefanie Gauguet, Neeraj K. Surana, Raina N. Fichorova, Abirami Kugadas, Saiprasad Sankaranarayanan, Ryan C. Kunz, Stig Hill Christiansen
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Eye Diseases
genetic structures
Neutrophils
Eye Infections
Gut flora
Pathology and Laboratory Medicine
Cornea
White Blood Cells
0302 clinical medicine
Animal Cells
Antibiotics
Medicine and Health Sciences
lcsh:QH301-705.5
Antimicrobials
Pseudomonas Aeruginosa
Drugs
Genomics
3. Good health
Bacterial Pathogens
Medical Microbiology
Cellular Types
Pathogens
Anatomy
Research Article
lcsh:Immunologic diseases. Allergy
Immune Cells
Ocular Anatomy
Immunology
Microbial Genomics
Biology
Microbiology
Keratitis
03 medical and health sciences
Immune system
Immunity
Ocular System
Virology
Pseudomonas
Microbial Control
medicine
Genetics
Microbiome
Molecular Biology
Microbial Pathogens
Pharmacology
Innate immune system
Blood Cells
Bacteria
Organisms
Biology and Life Sciences
Cell Biology
Eye infection
medicine.disease
biology.organism_classification
eye diseases
Contact lens
Ophthalmology
030104 developmental biology
lcsh:Biology (General)
030221 ophthalmology & optometry
Eyes
Parasitology
sense organs
lcsh:RC581-607
Head
Zdroj: PLoS Pathogens, Vol 12, Iss 9, p e1005855 (2016)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular susceptibility to Pseudomonas aeruginosa–induced keratitis. We find that in health, the presence of microbiota strengthened the ocular innate immune barrier by significantly increasing the concentrations of immune effectors in the tear film, including secretory IgA and complement proteins. Consistent with this view, Swiss Webster (SW) mice that are typically resistant to P. aeruginosa–induced keratitis become susceptible due to the lack of microbiota. This was exemplified by increased corneal bacterial burden and elevated pathology of the germ free (GF) mice when compared to the conventionally maintained SW mice. The protective immunity was found to be dependent on both eye and gut microbiota with the eye microbiota having a moderate, but significant impact on the resistance to infection. These events were IL-1ß–dependent as corneal IL-1ß levels were decreased in the infected GF and antibiotic-treated mice when compared to the SPF controls, and neutralization of IL-1ß increased the ocular bacterial burden in the SPF mice. Monocolonizing GF mice with Coagulase Negative Staphylococcus sp. isolated from the conjunctival swabs was sufficient to restore resistance to infection. Cumulatively, these data underline a previously unappreciated role for microbiota in regulating susceptibility to ocular keratitis. We predict that these results will have significant implications for contact lens wearers, where alterations in the ocular commensal communities may render the ocular surface vulnerable to infections.
Author Summary Contact lens wear is associated with frequent Pseudomonas aeruginosa–induced keratitis, however the reasons for this association remain unclear. Recent genomics–based approaches revealed that contact lens wearers harbor altered ocular commensal communities when compared to non-lens wearers raising important questions, namely, does wearing of contact lenses increase the frequency of keratitis in patients due to contamination of the contact lenses with species derived from the skin or does ocular microbiota exert immune functions that are required for the maintenance of ocular health? We demonstrate a clear role for ocular microbiota in regulating protection against Pseudomonas aeruginosa–induced infections. At the ocular surface, commensal bacteria provide signals that regulate the magnitude of neutrophil recruitment during infection. These events may be driven by a frequent gram-positive commensal–Coagulase Negative Staphylococcus (CNS) sp. In addition to the impact of ocular microbiota, there is an important contribution of gut microbiota that stimulate neutrophil development in the bone marrow, thereby regulating the pool of mature neutrophils and their activation state. Cumulatively, these data show for the first time a role for microbiota in regulating the susceptibility to P. aeruginosa–keratitis.
Databáze: OpenAIRE
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