Idioma:

Pulmonary infection with hypervirulent Mycobacteria reveals a crucial role for the P2X7 receptor in aggressive forms of tuberculosis

Amaral, Eduardo P ; Ribeiro, Simone C M ; Lanes, Verônica R ; Almeida, Fabrício M ; de Andrade, Marcelle R M ; Bomfim, Caio Cesar Barbosa ; Salles, Erika M ; Bortoluci, Karina R ; Coutinho-Silva, Robson ; Hirata, Mario H ; Alvarez, José M ; Lasunskaia, Elena B ; D'Império-Lima, Maria Regina Sassetti, Christopher M.

PLoS pathogens, 2014-07, Vol.10 (7), p.e1004188-e1004188 [Periódico revisado por pares]

United States: Public Library of Science

Texto completo disponível

Citações Citado por

Enviar para

Título:
Pulmonary infection with hypervirulent Mycobacteria reveals a crucial role for the P2X7 receptor in aggressive forms of tuberculosis
Autor: Amaral, Eduardo P ; Ribeiro, Simone C M ; Lanes, Verônica R ; Almeida, Fabrício M ; de Andrade, Marcelle R M ; Bomfim, Caio Cesar Barbosa ; Salles, Erika M ; Bortoluci, Karina R ; Coutinho-Silva, Robson ; Hirata, Mario H ; Alvarez, José M ; Lasunskaia, Elena B ; D'Império-Lima, Maria Regina
Sassetti, Christopher M.
Assuntos: Adenosine Triphosphate - immunology ; Animals ; Apoptosis ; B cells ; Bacteria ; Bacterial pneumonia ; Biology and Life Sciences ; Care and treatment ; Cytokines ; Development and progression ; Disease ; Drug therapy ; Experiments ; Gangrene ; Health aspects ; Humans ; Immune system ; Infections ; Macrophages - immunology ; Macrophages - microbiology ; Macrophages - pathology ; Mice ; Mice, Knockout ; Mortality ; Mycobacterium bovis - immunology ; Mycobacterium bovis - pathogenicity ; Mycobacterium tuberculosis - immunology ; Mycobacterium tuberculosis - pathogenicity ; Physiological aspects ; Pneumonia ; Receptors, Purinergic P2X7 - genetics ; Receptors, Purinergic P2X7 - immunology ; Rodents ; Tuberculosis ; Tuberculosis, Pulmonary - genetics ; Tuberculosis, Pulmonary - immunology ; Tuberculosis, Pulmonary - pathology
É parte de: PLoS pathogens, 2014-07, Vol.10 (7), p.e1004188-e1004188
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceived and designed the experiments: EPA EBL MRDL. Performed the experiments: EPA MRMdA SCMR VRL FMA CCBB EMS EBL. Analyzed the data: EPA EBL MRDL. Contributed reagents/materials/analysis tools: KRB RCS MHH JMA EBL MRDL. Wrote the paper: EPA EBL MRDL.
EBL and MRDL are joint senior authors on this work.
The authors have declared that no competing interests exist.
Descrição: The purinergic P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine production and cell death. To investigate whether the innate immune response to damage signals could contribute to the development of pulmonary necrotic lesions in severe forms of tuberculosis, disease progression was examined in C57BL/6 and P2X7R-/- mice that were intratracheally infected with highly virulent mycobacterial strains (Mycobacterium tuberculosis strain 1471 of the Beijing genotype family and Mycobacterium bovis strain MP287/03). The low-dose infection of C57BL/6 mice with bacteria of these strains caused the rapid development of extensive granulomatous pneumonia with necrotic areas, intense bacillus dissemination and anticipated animal death. In contrast, in P2X7R-/- mice, the lung pathology presented with moderate infiltrates of mononuclear leukocytes without visible signs of necrosis; the disease attenuation was accompanied by a delay in mortality. In vitro, the hypervirulent mycobacteria grew rapidly inside macrophages and induced death by a P2X7R-dependent mechanism that facilitated the release of bacilli. Furthermore, these bacteria were resistant to the protective mechanisms elicited in macrophages following extracellular ATP stimulation. Based on this study, we propose that the rapid intracellular growth of hypervirulent mycobacteria results in massive macrophage damage. The ATP released by damaged cells engages P2X7R and accelerates the necrotic death of infected macrophages and the release of bacilli. This vicious cycle exacerbates pneumonia and lung necrosis by promoting widespread cell destruction and bacillus dissemination. These findings suggest the use of drugs that have been designed to inhibit the P2X7R as a new therapeutic approach to treat the aggressive forms of tuberculosis.
Editor: United States: Public Library of Science
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Pulmonary infection with hypervirulent Mycobacteria reveals a crucial role for the P2X7 receptor in aggressive forms of tuberculosis

United States: Public Library of Science

Buscando em bases de dados remotas. Favor aguardar.