Use of flagellin to prevent and treat gram negative bacterial infection
The disclosure describes use of flagellin polypeptides to induce tolerance to gram negative bacteria, such as Pseudomonas aeruginosa , in order to alleviate the effects of the inflammatory response to bacterial infection in a patient. Also described are methods and compositions for treating and preventing keratitis, cystic fibrosis, asthma, and other diseases and conditions in which inflammation contributes to the pathology and symptoms.
1. A method of inducing immune tolerance to reduce local inflammation caused by an infective gram-negative bacteria in a subject to alleviate a disease or condition of the eye or the lung caused by the infective gram-negative bacteria, the method comprising locally administering to the epithelial cells of the eye or the lung of the subject an amount of a bacterial flagellin polypeptide wherein said amount is effective to induce immune self-tolerance to flagellin and immune tolerance to the infective gram-negative bacteria, and reduce local inflammation caused by the infective gram-negative bacteria in the subject.
2. The method of claim 1 wherein the disease or condition is selected from the group consisting of a corneal epithelial infection, and a lung epithelial infection.
3. The method of claim 2 wherein the gram negative bacterium is Pseudomonas aeruginosa.
4. The method of claim 3 , wherein the local administration is to the lung and the disease or condition is cystic fibrosis.
5. The method of claim 1 , wherein said flagellin polypeptide limits or eliminates multiplication of the gram-negative bacteria.
6. The method of claim 5 , wherein the local administration is to the eye and the disease or condition is bacterial keratitis.
7. The method of claim 5 , wherein the local administration is to the eye, the disease or condition is bacterial keratitis and the infective gram-negative bacteria is Pseudomonas aeruginosa.
8. The method of claim 5 , wherein the disease or condition is a pulmonary infection.
9. The method of claim 5 , wherein the disease or condition is selected from the group consisting of asthma, chronic obstructive pulmonary disease, and cystic fibrosis.