Mycobacterium tuberculosis expressing phospholipase C subverts PGE2 synthesis and induces necrosis in alveolar macrophages

BMC Microbiology

Lúcia H Faccioli³  Célio L Silva²  Sylvia C Leão¹  Priscilla AT Pereira³  Wendy M Rios²  Francisco WG Paula-Silva³  Milena S Espíndola²  Patricia A Assis² 

[1]Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

[2]Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

[3]Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av Cafe, s/n, Ribeirão Preto, SP 14040-903, Brazil

关键词: Prostaglandins;    Macrophage necrosis;    Cell death;    Phospholipase C;    Lipid mediator;    Mycobacterium;   

Others  :  1141045
DOI  :  10.1186/1471-2180-14-128

 received in 2013-11-15, accepted in 2014-05-06,  发布年份 2014

【 摘 要 】

Background

Phospholipases C (PLCs) are virulence factors found in several bacteria. In Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE₂, an essential factor in cell membrane protection.

Results

Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. The isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE₂ production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE₂ inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE₂ production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.

Conclusions

Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE₂ production.

【 授权许可】

   
2014 Assis et al.; licensee BioMed Central Ltd.

【 图 表 】

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