The truncated Rv2820c of Mycobacterium tuberculosis Beijing family augments intracellular survival of M. smegmatis by altering cytokine profile and inhibiting NO generation.
Infection, Genetics and Evolution(2018)
摘要
Genetic variations among genes of Mycobacterium tuberculosis may be associated with antigenic variation and immune evasion, which complicates the pathogenesis of M. tuberculosis. The hyper-virulent M. tuberculosis Beijing strains harbored several large sequence deletions, among which RD207 attributed to the deletion of CRISPR loci and several Cas genes. RD207 also gave rise to a truncated gene Rv2820c-Bj with 60% deletion in length at the 3′-end and a new 3′-end of five amino acid mutations. It has been reported that Rv2820c-Bj correlated with enhanced intracellular survival of M. smegmatis in macrophages when compared to its full-length counterpart Rv2820c in M. tuberculosis, however, the respective contribution of the truncation and the new 3′-end of Rv2820c-Bj to this enhancement was unclear. Here, by infecting THP-1 macrophages with Ms_Rv2820c-Bj, Ms_Rv2820c and MS_Rv2820c-Tr (expressing the truncated Rv2820c without five amino acid mutations at 3′-end), we found only Ms_Rv2820c-Bj was responsible for the enhancement of survival of M. smegmatis in macrophages. Furthermore, we detected that Ms_Rv2820c-Tr and Ms_Rv2820c-Bj induced similar cytokine profile and NO production after infection of macrophages, which was distinctly different from Ms_Rv2820c. However, Ms_Rv2820c-Bj evoked higher levels of interleukin-10 (IL-10) and lower levels of interleukin- 6 (IL-6), interleukin-1β (IL-1β) and interleukin-12 (IL-12) in infected THP-1 macrophages than Ms_Rv2820c-Tr. Accordingly, we concluded that the new 3′-end of Rv2820c-Bj was important to dampen host defense and enhance the intracellular survival of M. smegmatis.
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关键词
RD207,CRISPR,Cas genes,iNOS,NO,IL-10,IL-6,IL-1β,IL-12
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