Proline-Glutamate/Proline-Proline-Glutamate (PE/PPE) proteins of Mycobacterium tuberculosis: The multifaceted immune-modulators

Medha, *; Sharma, Sadhna; Sharma, Monika

doi:10.1016/j.actatropica.2021.106035

Cited by 17 publications

(16 citation statements)

References 140 publications

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“…Up-regulation of pro-inflammatory cytokines, such as IL-6, IL-12p40, IL-1β and TNF-α, accompanied by pathogen survival was detected in response to PPE32 and PPE60 [ 38 , 56 ]. M. smegmatis expressing Rv1195 encoded PE13 was shown to increase IL-6 and IL-1β from infected macrophages through the p38-ERK-NF-κB host-signaling pathway [ 57 ]. Rv0335c encoded PE6, a secretory protein of M.tb , subdues immune responses by promoting the secretion of IL-12, IL-6 and TNF-α, most important pro-inflammatory cytokines from host macrophages in TLR4 and Myd88 dependent manner [ 58 ].…”

Section: Ambiguous Immune Responses Of Pe/ppe/pe_pgrs Proteins Of Mtbmentioning

confidence: 99%

“…Rv0335c encoded PE6, a secretory protein of M.tb , subdues immune responses by promoting the secretion of IL-12, IL-6 and TNF-α, most important pro-inflammatory cytokines from host macrophages in TLR4 and Myd88 dependent manner [ 58 ]. IFN-γ and IL-2 have been shown to be upregulated from polarized Th-2 cells and pro-inflammatory cytokines (TNF-α, IL-6 and IL-12p40) in response to PPE57 of M.tb [ 57 , 59 ]. PE3 was overexpressed during the chronic infection of M.tb and immunization with PE3 results in elevated protective immune response.…”

Section: Ambiguous Immune Responses Of Pe/ppe/pe_pgrs Proteins Of Mtbmentioning

confidence: 99%

“…The role of PE_PGRS proteins in the immune evasion mechanism is attributed to varied and diverse patterns of the cytokine profile during M.tb infections [ 57 ]. While some of the PE_PGRS family of proteins, such as PE_PGRS5, PE_PGRS11, PE_PGRS17 and PE_PGRS30, evoke pro-inflammatory responses; others such as PE_PGRS26 are known to induce anti-inflammatory responses.…”

Section: Immune Evasion and Subversion Properties Of Pe_pgrs Proteins: A Possible Reflection Of Antigenic Variation Disordered Nature Andmentioning

confidence: 99%

“…Several members of the PE_PGRS protein family were shown to induce a wide range of contradictory T-cell and B-cell responses as described in earlier sections [ 100 ]. Such responses are not specific to this protein family, rather a generalized and diverse immune profile have been observed [ 57 ]. PE_PGRS11 and PE_PGRS17 proteins are involved in the activation and maturation of human dendritic cells and boost pro-inflammatory responses [ 49 ].…”

Section: Immune Evasion and Subversion Properties Of Pe_pgrs Proteins: A Possible Reflection Of Antigenic Variation Disordered Nature Andmentioning

confidence: 99%

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The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

Sharma

Alam

Ehtram

et al. 2022

IJMS

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Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.

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Section: Ambiguous Immune Responses Of Pe/ppe/pe_pgrs Proteins Of Mtbmentioning

confidence: 99%

Section: Ambiguous Immune Responses Of Pe/ppe/pe_pgrs Proteins Of Mtbmentioning

confidence: 99%

Section: Immune Evasion and Subversion Properties Of Pe_pgrs Proteins: A Possible Reflection Of Antigenic Variation Disordered Nature Andmentioning

confidence: 99%

Section: Immune Evasion and Subversion Properties Of Pe_pgrs Proteins: A Possible Reflection Of Antigenic Variation Disordered Nature Andmentioning

confidence: 99%

See 2 more Smart Citations

The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

Sharma

Alam

Ehtram

et al. 2022

IJMS

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“…The Proline-Glutamate (PE)/ Proline-Proline-Glutamate (PPE) proteins encoded within 7% of Mtb genome are exclusive to the pathogenicMycobacterium (Cole et al , 1998;Gey Van Pittius et al , 2006;McGuire et al , 2012). The PE -PGRS proteins of this family have been studied for their immunogenic potential and as modulators of host immune responses (Medha, Sharma and Sharma, 2021). Many PE PGRS proteins are still uncharacterized and therefore, investigating their role in Mtb pathogenesis and persistence poses an interesting research question.…”

Section: Introductionmentioning

confidence: 99%

Deciphering the role of PE_PGRS45 (Rv2615c) protein of Mycobacterium tuberculosis in host macrophage apoptosis: Possible effector for persistence

Sharma

Medha

Choudhary

et al. 2023

Preprint

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Mycobacterium tuberculosis has co-evolved with its host to evade and modulate host cellular processes. Few PE/PPE proteins of Mycobacterium have been reported to modulate cell death pathways and determine the infection outcome. This study investigates role of one such uncharacterized protein PE_PGRS45/Rv2615c in host cell death and immuno-modulation. In-silico analysis predicted similarity of Rv2615c with APAF1-apoptosome and involvement in Cysteine-type endo-peptidase activation during apoptosis. In-vitro experiments with THP-1 macrophages confirmed the Caspase-dependent apoptosis inducing potential of Rv2615c. Several PE_PGRS proteins have been reported to be TLR-agonist. Docking showed preferential binding of Rv2615c with TLR4 than TLR2. Up-regulation of TLR4-HLA-DR-MyD88-NF-ƙB-TNF‐α in Rv2615c-stimulated THP-1 macrophages was observed. To investigate the mechanism underpinning the apoptotic function, a thorough sequence scan of Rv2615c revealed the presence of eukaryotic CARD-like domain in it. In-silico studies showed binding affinity of Rv2615c’s CARD-like domain with APAF1-CARD and Caspase9-CARD, attributing Rv2615c’s role in apoptosis. Since, Rv2615c is reported to be upregulated in dormancy which suggest that it may be one of the unexplored effectors employed by Mtb for its persistence via silent cell-to-cell spread of infection by inducing macrophage apoptosis. Additionally, Rv2615c’s interaction with TLR4 implicates its engagement in host-pathogen interaction.

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Mycobacterium tuberculosis protein PPE15 (Rv1039c) possesses eukaryote-like SH3 domain that interferes with NADPH Oxidase assembly and Reactive Oxygen Species production

Priyanka,

Sharma,

Joshi

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Proline-Glutamate/Proline-Proline-Glutamate (PE/PPE) proteins of Mycobacterium tuberculosis: The multifaceted immune-modulators

Cited by 17 publications

References 140 publications

The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

Deciphering the role of PE_PGRS45 (Rv2615c) protein of Mycobacterium tuberculosis in host macrophage apoptosis: Possible effector for persistence

Mycobacterium tuberculosis protein PPE15 (Rv1039c) possesses eukaryote-like SH3 domain that interferes with NADPH Oxidase assembly and Reactive Oxygen Species production

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