Phagolysosome maturation of macrophages was reduced by PE_PGRS 62 protein expressing in Mycobacterium smegmatis and induced in IFN-γ priming.
Mycobacterium bovis parasitizes host macrophages and has developed strategies to survive within macrophages. Research on mycobacteria-specific PE_PGRS genes indicates that they code for cell surface proteins that may influence virulence. To further elucidate the molecular pathogenesis of tuberculosis and host response to M. bovis, we explored the mechanisms by which PE_PGRS62 protein increase persistence of mycobacterium within host macrophages. We found that the M. smegmatis strain expressing M. bovis PE_PGRS 62 protein reduced phagolysosome maturation in human macrophages, and significantly decreased the mRNA expression of IL-1β in a dose- and time-dependent. We identified that IFN-γ priming of macrophages immediately prior to infection with PE_PGRS62 expressing M. smegmantis, enhanced the maturation of phagolysosomes and induced IL-1β production both that the protein and mRNA levels and further activated the NF-κB pathway. Overall, we demonstrated that PE_PGRS62 protein altered the immune environment of the host cells, which suggested that the pathogenic PE_PGRS62 protein altering the immune mechanism might be involved in the pathogenesis of mycobacterial disease and hence influenced host cell responses to M. bovis infection.
The State Key Lab of Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National TSE Lab, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China. hy831119@163.com
Ying
Y
Huang
Xiangmei
X
Zhou
Yu
Y
Bai
Lifeng
L
Yang
Xiaomin
X
Yin
Zhigang
Z
Wang
Deming
D
Zhao
D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology*; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology / Q000382:microbiology; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014169:Transformation, Bacterial; D014380:Tuberculosis, Bovine / Q000276:immunology / Q000382:microbiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D053583:Interleukin-1beta; D008565:Membrane Proteins; D016328:NF-kappa B; C440642:PE-PGRS protein, Mycobacterium; D011994:Recombinant Proteins; D007371:Interferon-gamma