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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

P2X7 receptor in Bone Marrow-Derived cells aggravates Tuberculosis caused by hypervirulent Mycobacterium bovis

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Barbosa Bomfim, Caio Cesar ; Amaral, Eduardo Pinheiro ; Cassado, Alexandra dos Anjos ; Salles, Erika Machado ; do Nascimento, Rogerio Silva ; Lasunskaia, Elena ; Hirata, Mario Hiroyuki ; Alvarez, Jose Maria ; D'Imperio-Lima, Maria Regina
Total Authors: 9
Document type: Journal article
Source: FRONTIERS IN IMMUNOLOGY; v. 8, APR 13 2017.
Web of Science Citations: 5

Tuberculosis (TB) remains a serious public health problem despite the great scientific advances in the recent decades. We have previously shown that aggressive forms of TB caused by hypervirulent strains of Mycobacterium tuberculosis and Mycobacterium bovis are attenuated in mice lacking the P2X7 receptor, an ion channel activated by extracellular ATP. Therefore, P2X7 receptor is a potential target for therapeutic intervention. In vitro, hypervirulent mycobacteria cause macrophage death by a P2X7-dependent mechanism that facilitates bacillus dissemination. However, as P2X7 receptor is expressed in both bone marrow (BM)-derived cells and lung structural cells, several cellular mechanisms can operate in vivo. To investigate whether the presence of P2X7 receptor in BM-derived cells contributes to TB severity, we generated chimeric mice by adoptive transfer of hematopoietic cells from C57BL/6 or P2X7(-/-) mice into CD45.1 irradiated mice. After infection with hypervirulent mycobacteria (MP287/03 strain of M. bovis), P2X7(-/-)> CD45.1 mice recapitulated the TB resistance observed in P2X7(-/-)mice. These chimeric mice showed lower lung bacterial load and attenuated pneumonia compared to C57BL/6> CD45.1 mice. Lung necrosis and bacterial dissemination to the spleen and liver were also reduced in P2X7(-/-)> CD45.1 mice compared to C57BL/6> CD45.1 mice. Furthermore, an immature-like myeloid cell population showing a Ly6G(int) phenotype was observed in the lungs of infected C57BL/6 and C57BL/6> CD45.1 mice, whereas P2X7(-/-)and P2X7(-/-)> CD45.1 mice showed a typical neutrophil (Ly6G(hi)) population. This study clearly demonstrates that P2X7 receptor in BM-derived cells plays a critical role in the progression of severe TB. (AU)

FAPESP's process: 12/22587-0 - Role of P2X7 receptor in modulation of lung immune response induced by hypervirulent mycobacteria
Grantee:Caio César Barbosa Bomfim
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 14/22986-8 - Role of myeloid derived suppressor cells and its purinergic regulation in severe tuberculosis
Grantee:Caio César Barbosa Bomfim
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis
Grantee:Maria Regina D'Império Lima
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/07140-2 - Role of inflammasomas in the pathogenesis of tuberculosis caused by hypervirulent clinical isolates of mycobacteria
Grantee:Maria Regina D'Império Lima
Support Opportunities: Regular Research Grants