PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2.
PE_PGRS represent a large family of proteins typical of pathogenic mycobacteria whose members are characterized by an N-terminal PE domain followed by a large Gly-Ala repeat-rich C-terminal domain. Despite the abundance of PE_PGRS-coding genes in the Mycobacterium tuberculosis (Mtb) genome their rol...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4792380?pdf=render |
| _version_ | 1819154514527125504 |
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| author | Ivana Palucci Serena Camassa Alessandro Cascioferro Michela Sali Saber Anoosheh Antonella Zumbo Mariachiara Minerva Raffaella Iantomasi Flavio De Maio Gabriele Di Sante Francesco Ria Maurizio Sanguinetti Giorgio Palù Michael J Brennan Riccardo Manganelli Giovanni Delogu |
| author_facet | Ivana Palucci Serena Camassa Alessandro Cascioferro Michela Sali Saber Anoosheh Antonella Zumbo Mariachiara Minerva Raffaella Iantomasi Flavio De Maio Gabriele Di Sante Francesco Ria Maurizio Sanguinetti Giorgio Palù Michael J Brennan Riccardo Manganelli Giovanni Delogu |
| author_sort | Ivana Palucci |
| collection | DOAJ |
| description | PE_PGRS represent a large family of proteins typical of pathogenic mycobacteria whose members are characterized by an N-terminal PE domain followed by a large Gly-Ala repeat-rich C-terminal domain. Despite the abundance of PE_PGRS-coding genes in the Mycobacterium tuberculosis (Mtb) genome their role and function in the biology and pathogenesis still remains elusive. In this study, we generated and characterized an Mtb H37Rv mutant (MtbΔ33) in which the structural gene of PE_PGRS33, a prototypical member of the protein family, was inactivated. We showed that this mutant entered macrophages with an efficiency up to ten times lower than parental or complemented strains, while its efficiency in infecting pneumocytes remained unaffected. Interestingly, the lack of PE_PGRS33 did not affect the intracellular growth of this mutant in macrophages. Using a series of functional deletion mutants of the PE_PGRS33 gene to complement the MtbΔ33 strain, we demonstrated that the PGRS domain is required to mediate cell entry into macrophages, with the key domain encompassing position 140-260 amino acids of PE_PGRS33. PE_PGRS33-mediated entry into macrophages was abolished in TLR2-deficient mice, as well as following treatment with wortmannin or an antibody against the complement receptor 3 (CR3), indicating that PE_PGRS33-mediated entry of Mtb in macrophages occurs through interaction with TLR2. |
| first_indexed | 2024-12-22T15:22:18Z |
| format | Article |
| id | doaj.art-43ad2b54e1de4bb786c256649dcc92bf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T15:22:18Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-43ad2b54e1de4bb786c256649dcc92bf2022-12-21T18:21:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015080010.1371/journal.pone.0150800PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2.Ivana PalucciSerena CamassaAlessandro CascioferroMichela SaliSaber AnooshehAntonella ZumboMariachiara MinervaRaffaella IantomasiFlavio De MaioGabriele Di SanteFrancesco RiaMaurizio SanguinettiGiorgio PalùMichael J BrennanRiccardo ManganelliGiovanni DeloguPE_PGRS represent a large family of proteins typical of pathogenic mycobacteria whose members are characterized by an N-terminal PE domain followed by a large Gly-Ala repeat-rich C-terminal domain. Despite the abundance of PE_PGRS-coding genes in the Mycobacterium tuberculosis (Mtb) genome their role and function in the biology and pathogenesis still remains elusive. In this study, we generated and characterized an Mtb H37Rv mutant (MtbΔ33) in which the structural gene of PE_PGRS33, a prototypical member of the protein family, was inactivated. We showed that this mutant entered macrophages with an efficiency up to ten times lower than parental or complemented strains, while its efficiency in infecting pneumocytes remained unaffected. Interestingly, the lack of PE_PGRS33 did not affect the intracellular growth of this mutant in macrophages. Using a series of functional deletion mutants of the PE_PGRS33 gene to complement the MtbΔ33 strain, we demonstrated that the PGRS domain is required to mediate cell entry into macrophages, with the key domain encompassing position 140-260 amino acids of PE_PGRS33. PE_PGRS33-mediated entry into macrophages was abolished in TLR2-deficient mice, as well as following treatment with wortmannin or an antibody against the complement receptor 3 (CR3), indicating that PE_PGRS33-mediated entry of Mtb in macrophages occurs through interaction with TLR2.http://europepmc.org/articles/PMC4792380?pdf=render |
| spellingShingle | Ivana Palucci Serena Camassa Alessandro Cascioferro Michela Sali Saber Anoosheh Antonella Zumbo Mariachiara Minerva Raffaella Iantomasi Flavio De Maio Gabriele Di Sante Francesco Ria Maurizio Sanguinetti Giorgio Palù Michael J Brennan Riccardo Manganelli Giovanni Delogu PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2. PLoS ONE |
| title | PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2. |
| title_full | PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2. |
| title_fullStr | PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2. |
| title_full_unstemmed | PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2. |
| title_short | PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2. |
| title_sort | pe pgrs33 contributes to mycobacterium tuberculosis entry in macrophages through interaction with tlr2 |
| url | http://europepmc.org/articles/PMC4792380?pdf=render |
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