Lower respiratory tract infection due to Pseudomonas aeruginosa has become increasingly challenging, resulting in a worse morbidity and mortality. Airway remodeling is a common phenomenon in this process, to which epithelial-mesenchymal transition (EMT) may contribute as an important promoter. Previous studies showed that epithelium-specific integrin αvβ6-mediated EMT was involved in pulmonary fibrosis via transforming growth factor-β1 (TGF-β1) signaling, but whether integrin αvβ6 plays a role in the P. aeruginosa-associated airway remodeling remains unknown. BEAS-2B cells were incubated with lipopolysaccharide (LPS) from P. aeruginosa in the presence or the absence of integrin αvβ6-blocking antibodies. Morphologic changes were observed by an inverted microscopy. The EMT markers were detected using Western blotting and immunofluorescence. The activation of TGF-β1-Smad2/3 signaling pathway was assessed. Furthermore, matrix metalloproteinase (MMP)-2 and -9 in the medium were measured using ELISA. P. aeruginosa's LPS decreased the expression of the epithelial marker E-cadherin and promoted the mesenchymal markers, vimentin and α-smooth muscle actin in BEAS-2B cells. The expression of integrin αvβ6 was significantly increased during EMT process. Blocking integrin αvβ6 could attenuate P. aeruginosa's LPS-induced EMT markers' expression via TGF-β1-Smad2/3 signaling pathway. Furthermore, blocking integrin αvβ6 could prevent morphologic changes and oversecretion of MMP-2 and -9. Integrin αvβ6 mediates epithelial-mesenchymal transition in human bronchial epithelial cells induced by lipopolysaccharides of P. aeruginosa via TGF-β1-Smad2/3 signaling pathway and might be a promising therapeutic target for P. aeruginosa-associated airway remodeling.
- MeSH
- antigeny nádorové genetika metabolismus MeSH
- epitelo-mezenchymální tranzice * MeSH
- epitelové buňky cytologie účinky léků metabolismus MeSH
- integriny genetika metabolismus MeSH
- lidé MeSH
- lipopolysacharidy metabolismus MeSH
- matrixové metaloproteinasy genetika metabolismus MeSH
- protein Smad2 genetika metabolismus MeSH
- protein Smad3 genetika metabolismus MeSH
- pseudomonádové infekce genetika metabolismus mikrobiologie patofyziologie MeSH
- Pseudomonas aeruginosa metabolismus MeSH
- signální transdukce MeSH
- transformující růstový faktor beta1 genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The interleukin 17 (IL-17) cytokine and receptor family is central to antimicrobial resistance and inflammation in the lung. Mice lacking IL-17A, IL-17F, or the IL-17RA subunit were compared with wild-type mice for susceptibility to airway inflammation in models of infection and allergy. Signaling through IL-17RA was required for efficient microbial clearance and prevention of allergy; in the absence of IL-17RA, signaling through IL-17RC on epithelial cells, predominantly by IL-17F, significantly exacerbated lower airway Aspergillus or Pseudomonas infection and allergic airway inflammation. In contrast, following infection with the upper respiratory pathogen Staphylococcus aureus, the IL-17F/IL-17RC axis mediated protection. Thus, IL-17A and IL-17F exert distinct biological effects during pulmonary infection; the IL-17F/IL-17RC signaling axis has the potential to significantly worsen pathogen-associated inflammation of the lower respiratory tract in particular, and should be investigated further as a therapeutic target for treating pathological inflammation in the lung.
- MeSH
- alergie genetika imunologie mikrobiologie patologie MeSH
- Aspergillus imunologie MeSH
- aspergilóza genetika imunologie mikrobiologie patologie MeSH
- epitelové buňky imunologie mikrobiologie patologie MeSH
- interleukin-17 nedostatek genetika imunologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- náchylnost k nemoci MeSH
- plíce imunologie mikrobiologie patologie MeSH
- protein - isoformy nedostatek genetika imunologie MeSH
- pseudomonádové infekce genetika imunologie mikrobiologie patologie MeSH
- Pseudomonas imunologie MeSH
- receptory interleukinu-17 nedostatek genetika imunologie MeSH
- regulace genové exprese MeSH
- respirační sliznice imunologie mikrobiologie patologie MeSH
- signální transdukce MeSH
- stafylokokové infekce genetika imunologie mikrobiologie patologie MeSH
- Staphylococcus aureus imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In children with primary immunodeficiencies, the onset of symptoms precedes the diagnosis and the initiation of appropriate treatment by months or years. This delay in diagnosis is due to the fact that while these disorders are rare, some of the infections seen in immunodeficient patients are common. Defective antibody production represents the largest group among these disorders, with otitis, sinusitis and pneumonia as the most frequent initial manifestation. We performed a prospective study of humoral immunity in children hospitalized due to community-acquired pneumonia in tertiary care hospital. Out of 254 patients (131 boys, 123 girls, median age 4.5 years) recruited over 3 years, we found 2 boys (age 11 and 21 months) lacking serum immunoglobulins and circulating B cells. Subsequent genetic analysis confirmed diagnosis of X-linked agammaglobulinemia. Despite their immunodeficiency, the pneumonia was uncomplicated in both patients and did not call for immunological evaluation. However, the immunoglobulin screening at admission allowed for an early diagnosis of the immunodeficiency and timely initiation of immunoglobulin substitution, the key prerequisite for a favorable course of the disease.Simple and inexpensive immuno-globulin measurement during the manage-ment of hospitalized children with community-acquired pneumonia may help in early identification of patients with compromised humoral immunity and prevent serious complications.
- MeSH
- agamaglobulinemie diagnóza genetika imunologie terapie MeSH
- B-lymfocyty imunologie MeSH
- bakteriální pneumonie diagnóza genetika imunologie terapie MeSH
- časná diagnóza MeSH
- centra terciární péče MeSH
- genetické nemoci vázané na chromozom X diagnóza genetika imunologie terapie MeSH
- genetické testování * MeSH
- imunoglobuliny krev MeSH
- infekce získané v komunitě diagnóza genetika imunologie terapie MeSH
- kojenec MeSH
- lidé MeSH
- oportunní infekce diagnóza genetika imunologie terapie MeSH
- pasivní imunizace MeSH
- počet lymfocytů MeSH
- příjem pacientů * MeSH
- prognóza MeSH
- prospektivní studie MeSH
- pseudomonádové infekce diagnóza genetika imunologie terapie MeSH
- Pseudomonas aeruginosa * MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
Pacienti s cystickou fibrózou (CF) jsou náchylní k chronickým infekcím dýchacích cest, které zásadním způsobem ovlivňují jejich prognózu. Mezi nejzávažnější původce těchto infekcí patří bakterie komplexu Burkholderia cepacia a Pseudomonas aeruginosa, které navíc hrozí epidemickým rozsevem infekce v CF populaci. Z tohoto důvodu je důležité umět nejen časně a spolehlivě takové patogeny diagnostikovat, ale též určit, zda mají schopnost se mezi pacienty přenášet. Molekulárně genetické metody používané pro potřeby mikrobiologické diagnostiky umožňují s vysokou citlivostí detekovat komplex B. cepacia a zároveň určit jeho příslušnost k jednomu z devíti druhů. Genotypizační techniky vedou k identifikaci rizikových kmenů, které se mohou v CF populaci šířit. Pražské CF centrum se již více než jedno desetiletí potýká s mimořádnou epidemií infekce komplexem B. cepacia, za kterou je zodpovědný epidemický kmen ST-32. Pokles incidence pozorovaný v současnosti je velmi pravděpodobně výsledkem dodržování přísného protiepidemického režimu, nad jehož efektivitou bdí mikrobiologie používající moderní diagnostické přístupy.
Patients with cystic fibrosis (CF) are susceptible to chronic respiratory infections that considerably affect their long-term prognosis. Burkholderia cepacia complex and Pseudomonas aeruginosa are the most severe pathogens that can cause epidemic outbreaks within a CF population. To prevent their potential spread, early and reliable diagnostics along with transmissible strain identification is required. Molecular genetic methods allow highly sensitive and specific detection of bacteria belonging to B. cepacia complex and their speciation. Furthermore, the typing techniques help identify the strains capable of transmission among patients. The Prague CF Centre has been combating the widespread infection of B. cepacia complex caused by the strain ST-32 for more than 10 years. The current drop in its incidence is a likely consequence of strict infection control, which is monitored by applying molecular microbiological tools.
- MeSH
- Burkholderia cepacia genetika imunologie patogenita MeSH
- cystická fibróza diagnóza komplikace terapie MeSH
- financování organizované MeSH
- genotyp MeSH
- infekce bakteriemi rodu Burkholderia diagnóza genetika komplikace MeSH
- infekce dýchací soustavy diagnóza prevence a kontrola přenos MeSH
- lidé MeSH
- mikrobiologické techniky metody využití MeSH
- pseudomonádové infekce diagnóza genetika komplikace MeSH
- Pseudomonas aeruginosa genetika imunologie patogenita MeSH
- Check Tag
- lidé MeSH