Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE_PGRS47

Saini, Neeraj Kumar; Baena, Andrés; Ng, Tony W.; Venkataswamy, Manjunatha M.; Kennedy, Steven C.; Kunnath-Velayudhan, Shajo; Carreño, Leandro J.; Xu, Jiayong; Chan, John; Larsen, Michelle H.; Jacobs, William R.; Porcelli, Steven A.

doi:10.1038/nmicrobiol.2016.133

Cited by 152 publications

(161 citation statements)

References 52 publications

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“…This notion is supported by several reports implicating various mycobacterial virulence factors as mediators of this inhibition . Besides promoting the accumulation of nutrients, blocking autophagic processes is believed to benefit intracellular pathogens including M. tuberculosis by limiting the presentation of its antigens to T cells by MHC class II . The M. tuberculosis protein PE_PGRS47A was recently identified in a genome‐wide screen for genetic loci of M. tuberculosis that interfere with MHC class II restricted antigen presentation .…”

Section: Introductionmentioning

confidence: 85%

Mycobacterium tuberculosis: Rewiring host cell signaling to promote infection

Stutz

Clark

Doerflinger

et al. 2017

Journal of Leukocyte Biology

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The ability of Mycobacterium tuberculosis to cause disease hinges upon successfully thwarting the innate defenses of the macrophage host cell. The pathogen's trump card is its armory of virulence factors that throw normal host cell signaling into disarray. This process of subverting the macrophage begins upon entry into the cell, when M. tuberculosis actively inhibits the fusion of the bacilli-laden phagosomes with lysosomes. The pathogen then modulates an array of host signal transduction pathways, which dampens the macrophage's host-protective cytokine response, while simultaneously adapting host cell metabolism to stimulate lipid body accumulation. Mycobacterium tuberculosis also renovates the surface of its innate host cells by altering the expression of key molecules required for full activation of the adaptive immune response.Finally, the pathogen coordinates its exit from the host cell by shifting the balance from the hostprotective apoptotic cell death program toward a lytic form of host cell death. Thus, M. tuberculosis exploits its extensive repertoire of virulence factors in order to orchestrate the infection process to facilitate its growth, dissemination, and entry into latency. This review offers critical insights into the most recent advances in our knowledge of how M. tuberculosis manipulates host cell signaling. An appreciation of such interactions between the pathogen and host is critical for guiding novel therapies and understanding the factors that lead to the development of active disease in only a subset of exposed individuals. K E Y W O R D Shost-pathogen interactions, virulence factors, macrophages

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Section: Introductionmentioning

confidence: 85%

Mycobacterium tuberculosis: Rewiring host cell signaling to promote infection

Stutz

Clark

Doerflinger

et al. 2017

Journal of Leukocyte Biology

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show abstract

“…Also, disruption of the PE_PGRS47 (Rv2741) gene led to attenuated growth of M. tuberculosis in vitro and in vivo , and the PE_PGRS47 mutant showed enhanced major histocompatibility complex (MHC) class II-restricted antigen presentation (45). Deletion of PE_PGRS47 implicated this protein in the inhibition of autophagy in infected-host phagocytes.…”

Section: Function Location and Immunogenicity Of Pe/ppesmentioning

confidence: 99%

The Enigmatic PE/PPE Multigene Family of Mycobacteria and Tuberculosis Vaccination

Brennan

2017

Infect Immun

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The genome of Mycobacterium tuberculosis, the bacterium responsible for the disease tuberculosis, contains an unusual family of abundant antigens (PE/PPEs). To date, certain members of this multigene family occur only in mycobacteria that cause disease. It is possible that the numerous proteins encoded by these mycobacterial genes dictate the immune pathogenesis of this bacterial pathogen. There is also evidence that some of these antigens are present at the cell surface and that they affect the pathology and immunology of the organism in many ways. Also, they elicit both antibodies and T cells, they may be involved in antigenic variation, and they may be good candidates for vaccines and drugs. However, since they are plentiful and extremely homologous, these PE/PPEs are very challenging to study, and it is difficult to be certain what role(s) they have in the pathogenesis of tuberculosis. Consequently, how to develop treatments like vaccines using these antigens as candidates is complex.

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“…However, MTB can hinder oxidative stress, apoptosis and autophagy as well as inhibits the synthesis of histocompatibility complex molecules and thus affects antigen presentation. These mechanisms inhibit and resist the macrophages' natural immune killing and specific immune response, so as to help MTB escape from the body's immune killing . Therefore, a full understanding of the immune response mechanism of MTB infection has important theoretical significance for the clinical diagnosis as well as the research of new TB vaccine and immunotherapy .…”

Section: Introductionmentioning

confidence: 99%

STAT1 and its related molecules as potential biomarkers in Mycobacterium tuberculosis infection

Zhang

et al. 2020

J Cellular Molecular Medi

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Tuberculosis (TB) is a severe infectious disease that seriously endangers human health. The immune defence mechanism of the body against TB is still unclear. The purpose of this study was to find the key molecules involved in the immune defence response during TB infection, and provide reference for the treatment of TB and further understanding of the immune defence mechanism of the body. Data from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456 were downloaded from GEO data sets for analysis, and a total of 192 differentially expressed genes were screened out. Most of these genes are enriched in the interferon signalling pathway and are defence response–related. We also found that STAT1 plays an important role in the immune defence of TB infection and it is one of the key genes related to interferon signalling pathway. STAT1‐related molecules including hsa‐miR‐448, hsa‐miR‐223‐3p, SAMD8_hsa_circRNA 994 and TWF1_hsa_circRNA 9897 were therefore screened out. Furthermore, expression levels of hsa‐miR‐448 and hsa‐miR‐223‐3p were then verified by qRT‐PCR. Results showed that both hsa‐miR‐448 and hsa‐miR‐223‐3p were down‐regulated in plasma from patients with pulmonary TB. Taken together, our data indicate that an mRNA‐miRNA‐circRNA interaction chain may play an important role in the infection of MTB, and STAT1 and related molecules including hsa‐miR‐223‐3p, has‐miR‐448, SAMD8_hsa_circRNA994 and TWF1_hsa_circRNA9897 were identified as potential biomarkers in the development of active TB.

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Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE_PGRS47

Cited by 152 publications

References 52 publications

Mycobacterium tuberculosis: Rewiring host cell signaling to promote infection

Mycobacterium tuberculosis: Rewiring host cell signaling to promote infection

The Enigmatic PE/PPE Multigene Family of Mycobacteria and Tuberculosis Vaccination

STAT1 and its related molecules as potential biomarkers in Mycobacterium tuberculosis infection

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