Background: Ever since its discovery the mycobacterial proline-proline-glutamic acid (PPE) family of proteins has generated a huge amount of interest. Understanding the role of these proteins in the pathogenesis of Mycobacterium tuberculosis (Mtb) is important. We have demonstrated earlier that the PPE18 protein of Mtb induces IL-10 production in macrophages with subsequent downregulation of pro-inflammatory cytokines like IL-12 and TNF-α and favors a T-helper (Th) 2-type of immune response.
Methodology/principal Findings: Using a ppe18 genetic knock-out Mtb strain, we have now carried out infection studies in mice to understand the role of PPE18 in Mtb virulence. The studies reveal that lack of PPE18 leads to attenuation of Mtb in vivo. Mice infected with the ppe18 deleted strain have reduced infection burden in lung, liver and spleen and have better survival rates compared to mice infected with the wild-type Mtb strain.
Conclusions/significance: Taken together our data suggest that PPE18 could be a crucial virulence factor for intracellular survival of Mtb.
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Indian J Tuberc
October 2022
Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China. Electronic address:
Background: Tuberculosis (TB) is a global infectious disease, but there is no ideal vaccine against TB except the Bacille Calmette-Guérin (BCG) vaccine.
Methods: Herein, 25 candidate peptides were predicted from four antigens of Mycobacterium tuberculosis based on their high-affinity binding capacity for the human leukocyte antigen (HLA) DRB1∗0101. Three T-helper 1 (Th1) immunodominant peptides (Ag85B, CFP21, and PPE18) were identified by ELISPOT assays in the humanized C57BL/6 mice.
Front Microbiol
January 2021
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States.
Recent advancements in vaccinology have led to the development of the M72/AS01E subunit vaccine, of which the major component is the (MTB) PPE18 protein. Previous studies have demonstrated the genetic variability of the gene encoding PPE18 protein and the resulting peptide changes in diverse clinical strains of MTB; however, none have modeled the structural changes resulting from these peptide changes and their immunological implications. In this study, we investigated the structural predictions of 29 variant PPE18 proteins previously reported.
View Article and Find Full Text PDFJ Immunol
September 2016
Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad 500 001, India; and
As pathogen-associated molecular pattern sensors, the TLRs can detect diverse ligands to elicit either proinflammatory or anti-inflammatory responses, but the mechanism that dictates such contrasting immune responses is not well understood. In this work, we demonstrate that proline-proline-glutamic acid (PPE)17 protein of Mycobacterium tuberculosis induces TLR1/2 heterodimerization to elicit proinflammatory-type response, whereas PPE18-induced homodimerization of TLR2 triggers anti-inflammatory type responses. Ligation of TLR1/2 caused an increased recruitment of IL-1R-associated kinase (IRAK)1, MyD88, and protein kinase C (PKC)ε to the downstream TLR-signaling complex that translocated PKCε into the nucleus in an IRAK1-dependent manner.
View Article and Find Full Text PDFBackground: Ever since its discovery the mycobacterial proline-proline-glutamic acid (PPE) family of proteins has generated a huge amount of interest. Understanding the role of these proteins in the pathogenesis of Mycobacterium tuberculosis (Mtb) is important. We have demonstrated earlier that the PPE18 protein of Mtb induces IL-10 production in macrophages with subsequent downregulation of pro-inflammatory cytokines like IL-12 and TNF-α and favors a T-helper (Th) 2-type of immune response.
View Article and Find Full Text PDFJ Biol Chem
May 2012
Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics, Gruhakalpa Building, Nampally, Hyderabad 500001, India.
Cells of the monocyte/macrophage lineage are shown to play a role in the pathogenesis of human immunodeficiency virus (HIV). The occurrence of HIV type 1 (HIV-1) infection is found to be accelerated in people infected with Mycobacterium tuberculosis, but the mechanism by which mycobacterial protein(s) induces HIV-1 LTR trans-activation is not clearly understood. We show here that the M.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!