Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration
| Autor: | Mark D Singh, Imke Mulder, Margaret I Delday, Seanin Mccluskey, Emma Raftis, Anna Ettorre, Philip Cowie |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Neutrophils medicine.medical_treatment lcsh:Medicine Bifidobacterium breve Article Mice 03 medical and health sciences medicine Animals Humans Eosinophilia lcsh:Science Lung Inflammation House dust mite Multidisciplinary biology medicine.diagnostic_test business.industry Pyroglyphidae lcsh:R FOXP3 Allergens respiratory system Eosinophil biology.organism_classification medicine.disease Asthma Gastrointestinal Microbiome respiratory tract diseases Biological Therapy Eosinophils Mice Inbred C57BL Disease Models Animal Treatment Outcome 030104 developmental biology Bronchoalveolar lavage medicine.anatomical_structure Cytokine Immunology Cytokines Female lcsh:Q medicine.symptom business Infiltration (medical) |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Asthma is a phenotypically heterogeneous disease. In severe asthma, airway inflammation can be predominantly eosinophilic, neutrophilic, or mixed. Only a limited number of drug candidates are in development to address this unmet clinical need. Live biotherapeutics derived from the gut microbiota are a promising new therapeutic area. MRx0004 is a commensal Bifidobacterium breve strain isolated from the microbiota of a healthy human. The strain was tested prophylactically and therapeutically by oral gavage in a house dust mite mouse model of severe asthma. A strong reduction of neutrophil and eosinophil infiltration was observed in lung bronchoalveolar lavage fluid following MRx0004 treatment. Peribronchiolar and perivascular immunopathology was also reduced. MRx0004 increased lung CD4+CD44+ cells and CD4+FoxP3+ cells and decreased activated CD11b+ dendritic cells. Cytokine analysis of lung tissue revealed reductions of pro-inflammatory cytokines and chemokines involved in neutrophil migration. In comparison, anti-IL-17 antibody treatment effectively reduced neutrophilic infiltration and increased CD4+FoxP3+ cells, but it induced lung eosinophilia and did not decrease histopathology scores. We have demonstrated that MRx0004, a microbiota-derived bacterial strain, can reduce both neutrophilic and eosinophilic infiltration in a mouse model of severe asthma. This novel therapeutic is a promising next-generation drug for management of severe asthma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|