Apoptosis triggered by Rv1818c, a PE family gene from Mycobacterium tuberculosis is regulated by mitochondrial intermediates in T cells

Balaji, Kithiganahalli Narayanaswamy; Goyal, Girija; Narayana, Y.; Srinivas, Madduri; Chaturvedi, Rashmi; Mohammad, Saleemulla

doi:10.1016/j.micinf.2006.11.013

Cited by 64 publications

(55 citation statements)

References 29 publications

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“…Interestingly, mycobacterial Ags have been shown to possess the potential of regulating immune responses in humans and animal models (31,26,63). Although mycobacteria reside within phagolysosomes, cell wall Ags including lipoarabinomannan, phosphatidyl-myoinositol mannosides, and PE_PGRS Ags are released and traffic out of the mycobacterial phagosome into endocytic compartments as well as gain access to the extracellular environment in the form of exocytosed vesicles (14,61,64,65). In this perspective, deciphering the interaction of cell wall Ags of pathogenic mycobacteria with human DCs is important to understand the molecular pathogenesis of tuberculosis and host response to mycobacteria and to conceive prospective vaccine candidates.…”

Section: Discussionmentioning

confidence: 99%

PE_PGRS Antigens ofMycobacterium tuberculosisInduce Maturation and Activation of Human Dendritic Cells

Bansal

Elluru

Narayana

et al. 2010

The Journal of Immunology

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105

102

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Section: Discussionmentioning

confidence: 99%

PE_PGRS Antigens ofMycobacterium tuberculosisInduce Maturation and Activation of Human Dendritic Cells

Bansal

Elluru

Narayana

et al. 2010

The Journal of Immunology

Self Cite

105

102

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“…In particular, the PE protein PE28 has been annotated as esxS in the tuberculist database, and is in operon with esxR and the PE/PPE genes PE29 and PPE48 . Like ESAT-6, the PE/PPE proteins are immunogenic and also cause host cell death [Balaji et al, 2007;Basu et al, 2007]. It has been hypothesized that primitive strains harboring the ESAT-6 -like gene cluster have duplicated and then diverged to a total of five clusters through the course of evolution [Gey van Pittius et al, 2006].…”

Section: Transcriptional Regulationmentioning

confidence: 99%

“…The existence of these genes was speculated from epidemiological studies and the discovery of genes with the repetitive sequence motifs -CG-GCGGCAA and -GCCGGTGTTG [Cousins et al, 1998;Kremer et al, 1999]. The PE/PPE family contributes to 10% of the coding capacity with largely unknown functions but speculated to confer antigenic variability [Karboul et al, 2008], evoke host immune responses [Chaitra et al, 2007a, b;Choudhary et al, 2003;Tundup et al, 2008], cause host cell death [Balaji et al, 2007;Basu et al, 2007] and to have diagnostic potential Choudhary et al, 2003;Tundup et al, 2008]. Structurally, the sequences of the PE/ PPE genes show an overall conservation ( fig.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of Mycobacterium tuberculosis PE/PPE Genes: A Molecular Switch to Virulence

Mohareer¹,

Tundup²,

Hasnain³

2011

Microb Physiol

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The PE/PPE family of proteins, which constitute 10% of the coding capacity of the mycobacterial genome, comprises a unique set of genes which have no known homologs and have expanded throughout their evolution. Their association with virulence has been implicated by several researchers in tuberculosis, but the molecular basis of their virulence is yet to be completely explored. PE/PPE genes are mostly associated with the pathogenic strains of mycobacteria as many of them are known to be deleted in non-pathogenic ones. The non-essentiality of these genes for their in vitrogrowth but essentiality during infection highlights their active role in the host-pathogen interaction and consequently virulence. Even within the different strains of pathogenic mycobacteria and clinical isolates, many of the PE/PPE genes show sequence variation, pointing to their importance in providing antigenic variations, and have also been speculated to perform varied roles by differential expression during host-pathogen interaction. The transcriptional regulators of these genes could therefore act as a molecular switch for the pathogenesis of Mycobacterium tuberculosis. This review focuses on the expression and regulation of PE/PPE genes in the context of infection and pathogenicity and discusses the potential of these proteins as drug targets.

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“…Secreted mycobacterial proteins have been a major focus of previous studies to identify immunogenic molecules (36,37). In addition, proteins associated with the bacterial cell wall or cell surface, such as the proline-glutamic acid and proline-proline-glutamic acid (PE/PPE) protein family in M. tuberculosis, induce cellmediated immunity (38)(39)(40). Secreted proteins of the Esx family, including CFP-10 and ESAT-6, have been shown to be dominant T cell antigens (40)(41)(42).…”

mentioning

confidence: 99%

Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4⁺T Cells

et al. 2017

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Tuberculosis (TB) due to Mycobacterium tuberculosis remains a major global infectious disease problem, and a more efficacious vaccine is urgently needed for the control and prevention of disease caused by this organism. We previously reported that a genetically modified strain of Mycobacterium smegmatis called IKEPLUS is a promising TB vaccine candidate. Since protective immunity induced by IKEPLUS is dependent on antigen-specific CD4 ϩ T cell memory, we hypothesized that the specificity of the CD4 ϩ T cell response was a critical feature of this protection. Using in vitro assays of interferon gamma production (enzyme-linked immunosorbent spot [ELISPOT] assays) by splenocytes from IKEPLUS-immunized C57BL/6J mice, we identified an immunogenic peptide within the mycobacterial ribosomal large subunit protein RplJ, encoded by the Rv0651 gene. In a complementary approach, we generated major histocompatibility complex (MHC) class II-restricted T cell hybridomas from IKEPLUS-immunized mice. Screening of these T cell hybridomas against IKE-PLUS and ribosomes enriched from IKEPLUS suggested that the CD4 ϩ T cell response in IKEPLUS-immunized mice was dominated by the recognition of multiple components of the mycobacterial ribosome. Importantly, CD4 ϩ T cells specific for mycobacterial ribosomes accumulate to significant levels in the lungs of IKEPLUSimmunized mice following aerosol challenge with virulent M. tuberculosis, consistent with a role for these T cells in protective host immunity in TB. The identification of CD4 ϩ T cell responses to defined ribosomal protein epitopes expands the range of antigenic targets for adaptive immune responses to M. tuberculosis and may help to inform the design of more effective vaccines against tuberculosis.

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Apoptosis triggered by Rv1818c, a PE family gene from Mycobacterium tuberculosis is regulated by mitochondrial intermediates in T cells

Cited by 64 publications

References 29 publications

PE_PGRS Antigens ofMycobacterium tuberculosisInduce Maturation and Activation of Human Dendritic Cells

PE_PGRS Antigens ofMycobacterium tuberculosisInduce Maturation and Activation of Human Dendritic Cells

Transcriptional Regulation of Mycobacterium tuberculosis PE/PPE Genes: A Molecular Switch to Virulence

Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4⁺T Cells

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Apoptosis triggered by Rv1818c, a PE family gene from Mycobacterium tuberculosis is regulated by mitochondrial intermediates in T cells

Cited by 64 publications

References 29 publications

PE_PGRS Antigens ofMycobacterium tuberculosisInduce Maturation and Activation of Human Dendritic Cells

PE_PGRS Antigens ofMycobacterium tuberculosisInduce Maturation and Activation of Human Dendritic Cells

Transcriptional Regulation of Mycobacterium tuberculosis PE/PPE Genes: A Molecular Switch to Virulence

Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4+T Cells

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Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4⁺T Cells