Ins and outs of <i>Mycobacterium tuberculosis</i> PPE family in pathogenesis and implications for novel measures against tuberculosis

Deng, Wanyan; Xie, Jianping

doi:10.1002/jcb.23449

Cited by 15 publications

(9 citation statements)

References 78 publications

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“…It is closely associated with the ESAT-6 secretion system and largely located in the cell wall or cell membrane; all members of this family are characterized by a conserved N-terminal and a variable C-terminal. The expression of PPE protein is temporally modulated and highly expressed during MTB persistence [124]. One member of the PPE family is Pro-Pro-Glu 38 (PPE38), which inhibits the transcription of genes encoding MHC class I and decreases the number of CD8 + T cells in the spleen, liver and lungs.…”

Section: Other Mechanisms Helping M Tuberculosis To Escape Immunementioning

confidence: 99%

The Immune Escape Mechanisms of Mycobacterium Tuberculosis

Zhai

Zhang

et al. 2019

IJMS

263

197

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Epidemiological data from the Center of Disease Control (CDC) and the World Health Organization (WHO) statistics in 2017 show that 10.0 million people around the world became sick with tuberculosis. Mycobacterium tuberculosis (MTB) is an intracellular parasite that mainly attacks macrophages and inhibits their apoptosis. It can become a long-term infection in humans, causing a series of pathological changes and clinical manifestations. In this review, we summarize innate immunity including the inhibition of antioxidants, the maturation and acidification of phagolysosomes and especially the apoptosis and autophagy of macrophages. Besides, we also elaborate on the adaptive immune response and the formation of granulomas. A thorough understanding of these escape mechanisms is of major importance for the prevention, diagnosis and treatment of tuberculosis.

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Section: Other Mechanisms Helping M Tuberculosis To Escape Immunementioning

confidence: 99%

The Immune Escape Mechanisms of Mycobacterium Tuberculosis

Zhai

Zhang

et al. 2019

IJMS

263

197

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“…Many other PE/PPE proteins also induce anti‐inflammatory cytokine signalling (Balaji et al ., ; Basu et al ., ; Nair et al ., ; Bansal et al ., 2010a,b; Beaulieu et al ., ). Comprehensive reviews of how PE/PPE proteins modulate host immune responses can be found elsewhere (Sampson, ; Akhter et al ., ; Deng and Xie, ). Although technical variations in the numerous published studies make it difficult to compare and interpret the results obtained, it is evident that several family members have the capacity to influence host immune responses.…”

Section: Pe/ppe Protein Family and Host Immune Response: A Complex Rementioning

confidence: 99%

Phylogeny to function: PE/PPE protein evolution and impact on Mycobacterium tuberculosis pathogenicity

Fishbein

Wyk

Warren

et al. 2015

Molecular Microbiology

203

199

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SummaryThe pe/ppe genes represent one of the most intriguing aspects of the Mycobacterium tuberculosis genome. These genes are especially abundant in pathogenic mycobacteria, with more than 160 members in M. tuberculosis. Despite being discovered over 15 years ago, their function remains unclear, although various lines of evidence implicate selected family members in mycobacterial virulence. In this review, we use PE/PPE phylogeny as a framework within which we examine the diversity and putative functions of these proteins. We report on the evolution and diversity of the respective gene families, as well as the implications thereof for function and host immune recognition. We summarize recent findings on pe/ppe gene regulation, also placing this in the context of PE/PPE phylogeny. We collate data from several large proteomics datasets, providing an overview of PE/PPE localization, and discuss the implications this may have for host responses. Assessment of the current knowledge of PE/PPE diversity suggests that these proteins are not variable antigens as has been so widely speculated; however, they do clearly play important roles in virulence. Viewing the growing body of pe/ppe literature through the lens of phylogeny reveals trends in features and function that may be associated with the evolution of mycobacterial pathogenicity.

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“…69 members of PPE multigene antigen family have been found exclusively among mycobacteria [3,4]. PPE family shares a conserved N-terminal around 110 and 180 amino acid residues and a significant variable C-terminal with both sequences and sizes [5].…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium TuberculosisPPE Family Protein Rv1808 Manipulates Cytokines Profile via Co-Activation of MAPK and NF-κB Signaling Pathways

Deng

Zeng

et al. 2014

Cell Physiol Biochem

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Background/Aims: Mycobacterium tuberculosis is an extremely successful intracellular pathogen armed with multiple tactics to subvert host immunity. PPE (Pro-Pro-Glu) family exclusively distributed in mycobacteria might be responsible for the virulence and pathogenicity of M.tuberculosis. The up-regulation of Rv1808 (PPE32) in many conditions prompted us to define its role in host innate immune response. Methods: The Rv1808 encoding gene was expressed in nonpathogenic fast growing Mycobacterium smegmatis, mycobacteria- Escherichia coli shuttle plasmid pNITmyc served as control. RT-PCR and ELISA were used to detect the transcription and translation of host cytokines in culture supernatant from macrophage incubated with purified Rv1808 protein. Pharmacological inhibitors were applied to confirm the specificity of the effector interfering of host signaling. Results: Recombinant Ms_Rv1808 survived better than Ms_pNITmyc within macrophage, accompanied by slightly higher host cell death. Rv1808 protein is associated with the cell wall and exposed on the cell surface. Physical binding of Rv1808 to TLR2 resulted in increase in the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokines tumor necrosis factor (TNF-a) and interleukin-6 (IL-6) possibly via co-activation of NF-κB and MAPK (p38MAPK, JNK and ERK) signalling. Conclusion: Cell wall associated Rv1808 protein manipulated the host cytokines via MAPK and NF-κB signaling pathways.

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Ins and outs of Mycobacterium tuberculosis PPE family in pathogenesis and implications for novel measures against tuberculosis

Cited by 15 publications

References 78 publications

The Immune Escape Mechanisms of Mycobacterium Tuberculosis

The Immune Escape Mechanisms of Mycobacterium Tuberculosis

Phylogeny to function: PE/PPE protein evolution and impact on Mycobacterium tuberculosis pathogenicity

Mycobacterium TuberculosisPPE Family Protein Rv1808 Manipulates Cytokines Profile via Co-Activation of MAPK and NF-κB Signaling Pathways

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