Inhibiting Adenosine Receptor Signaling Promotes Accumulation of Effector CD4+ T Cells in the Lung Parenchyma During Severe Tuberculosis.
J Infect Dis
; 219(6): 964-974, 2019 02 23.
Article
em En
| MEDLINE
| ID: mdl-30307561
ABSTRACT
BACKGROUND:
Tuberculous pneumonia, necrotic granulomatous lesions, and bacterial dissemination characterize severe forms of mycobacterial infection.METHODS:
To evaluate the pulmonary CD4+ T-cell response during severe tuberculosis, C57BL/6 mice were infected with approximately 100 bacilli of 3 hypervirulent mycobacterial isolates (Mycobacterium tuberculosis strain Beijing 1471 and Mycobacterium bovis strains B2 and MP287/03) or the H37Rv M tuberculosis strain as reference for mycobacterial virulence. Because high expression of both CD39 and CD73 ectonucleotidases was detected on parenchymal CD4+ T cells, we investigated whether CD4+ T-cell suppression in the context of severe disease was due to the extracellular adenosine accumulation that resulted from tissue damage.RESULTS:
Lowest expression of CD69, which is an activation marker implicated in maintaining cells in tissues, was observed in lungs from mice displaying the most severe pulmonary pathology. Reduced interferon (IFN)γ-producing CD4+ T cells were also found in the lung of these mice. Intranasal administration of the adenosine receptor antagonist caffeine substantially enhanced the frequency and number of parenchymal CD4+ T cells as well as both CD69 expression and IFNγ production.CONCLUSIONS:
These results indicate that adenosine, which may be generated by extracellular adenosine triphosphate degradation, impairs the parenchymal CD4+ T-cell response and contributes to the development of severe tuberculosis.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Tuberculose Pulmonar
/
Linfócitos T CD4-Positivos
/
Pulmão
Limite:
Animals
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil