Tuberculosis is an important chronic and often fatal infectious disease mainly caused by the bacterium Mycobacterium tuberculosis (Mtb). Mtb is one of the most successful pathogens that harbors several potential virulence factors not found in nonpathogenic mycobacteria. As the Mtb cell envelope is closely associated with its virulence and resistance, it is very important to understand the cell envelope for better treatment of causative pathogen. There is increasing evidence that Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins are the major effectors of virulence and persistence encoded in the Mtb H37Rv genome. However, the function of PE8 has not been explored to date. In this study, we heterologously expressed PE8 in nonpathogenic, fast-growing M. smegmatis to investigate the interaction between PE8 and the host to determine its possible biological functions. We found that recombinant M. smegmatis cells expressing PE8 were less susceptible to sodium dodecyl sulfate-induced surface stress compared with those expressing the empty vector, suggesting that PE8 may be involved in stress responses. In addition, macrophages infected with PE8-expressing M. smegmatis produced obviously lower levels of the proinflammatory factor IL-1β, IL-6, and TNF-α and higher levels of the inhibitory factor IL-10. We further found that PE8 promoted M. smegmatis survival within macrophages by inhibiting late apoptosis of macrophages. Collectively, selective targeting of the PE/PPE protein family offers an untapped opportunity to the development of more effective and safer drugs against Mtb infection.
Mycobacterium tuberculosis heat resistant antigen (MTB-HAg) is a polypeptide antigen released from Mycobacterium tuberculosis (MTB) H37Ra to the supernatant after being autoclaved at 121 DegreesCelsius for 20 minutes. γδ T cells are unconventional T cells widely distributed in non-lymphoid tissues. They secrete cytokines such as TNF-α and IFN-γ, and play an important role in the immune response against MTB infection. MTB-HAg can effectively stimulate the proliferation and activation of γδ T cells in vitro, enabling them to participate more efficiently in the anti-TB infection process. Therefore, MTB-HAg is a potential target for the design of novel TB vaccines or drugs. However, due to its complex composition, it is still unknown which component of MTB-HAg stimulates the anti-MTB infection function of γδ T cells.
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