TSLP induces neutrophil mediated killing of methicillin-resistant staphylococcus aureus
Inventors
Leonard, Warren Jaye • West, Erin Elizabeth • Spolski, Rosanne • Garcia, K. Christopher
Assignees
Leland Stanford Junior University • US Department of Health and Human Services
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Publication Number
US-10201591-B2
Publication Date
2019-02-12
Expiration Date
2036-11-07
Abstract
The invention provides a method of promoting the host defense of a patient to a bacterial infection comprising administering to a patient suffering or at risk of a bacterial infection, a pharmaceutical composition comprising an effective amount of the pleiotropic cytokine, thymic stromal lymphopoietin (TSLP) protein or polypeptide in an amount and at a location sufficient to promote the host defense of the patient to the bacterial infection. In a preferred embodiment, the bacterial infection is the infection of the patient with MRSA.The invention also provides a method of treating blood product, which comprises introducing a TSLP protein or polypeptide into such blood product, wherein the blood product is extracorporeal and comprises at least one neutrophil.
Core Innovation
The invention provides a method of promoting the host defense of a patient to a bacterial infection by administering to the patient a pharmaceutical composition comprising an effective amount of thymic stromal lymphopoietin (TSLP) protein or polypeptide. The administration is performed in an amount and at a location sufficient to promote the host defense of the patient to the bacterial infection, with a preferred embodiment targeting infections with methicillin-resistant Staphylococcus aureus (MRSA).
The invention also discloses a method of treating blood products comprising at least one neutrophil by introducing a TSLP protein or polypeptide into said extracorporeal blood product to enhance the neutrophil-mediated killing of bacterial pathogens such as MRSA.
The problem addressed by the invention is the increasing prevalence of antibiotic-resistant bacterial infections, including MRSA, which causes serious skin infections even in otherwise healthy individuals. Existing treatments are insufficient, and there is a critical need for methods and reagents that increase the effectiveness of treating MRSA and other bacterial infections by enhancing the host immune response. Understanding mechanisms regulating immune activation against MRSA could lead to new therapeutic targets.
Claims Coverage
The claims cover inventive features centered on methods to promote host defense against bacterial infections through TSLP protein or polypeptide administration, specifying particular bacterial infections and compositions.
Method of promoting host defense with TSLP against bacterial infections
Administering to a human patient suffering from or at risk of a bacterial infection a pharmaceutical composition comprising an effective amount of TSLP protein or polypeptide that comprises, consists essentially of, or consists of sequences selected from SEQ ID NOs:1-3 or 7-11 or their combinations, to promote host defense against infections caused by Staphylococcus aureus or Streptococcus pyogenes, including MRSA.
Formulations for targeted administration
Pharmaceutical compositions are formulated for topical application to barrier tissues (such as conjunctiva, nasal, oral, rectal, skin, or vaginal epithelium, whether intact or broken), to abscesses, or for parenteral, subcutaneous, intradermal, intramuscular, intraperitoneal, or intravenous administration.
The inventive claims encompass methods to enhance host defense against specific bacterial infections by administering defined TSLP proteins or polypeptides in effective formulations and dosages for treatment or prophylaxis, particularly targeting MRSA and related bacterial pathogens.
Stated Advantages
TSLP protein or polypeptide enhances neutrophil-mediated killing of MRSA and other bacterial pathogens both in vitro and in vivo.
Administration of TSLP reduces bacterial burden and inflammation in animal models of skin infection.
TSLP acts directly on neutrophils, increasing their antibacterial activity in a receptor-dependent manner.
TSLP enhances antibacterial killing rapidly through non-transcriptional mechanisms involving reactive oxygen species and complement system activation, providing potential therapeutic benefits.
Documented Applications
Treatment and prevention of MRSA infections through administration of TSLP to patients suffering from or at risk of MRSA infection.
Therapeutic use of TSLP in promoting host defense against infections with Staphylococcus aureus and Streptococcus pyogenes.
Treatment of extracorporeal blood products comprising neutrophils by introducing TSLP protein or polypeptide to enhance neutrophil antibacterial activity.
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