PE-PGRS33 contributes to Mycobacterium tuberculosis entry in macrophages through interaction with TLR2

Ivana Palucci, Michela Sali, Gabriele Di Sante, Francesco Ria, Maurizio Sanguinetti, Giovanni Delogu, Maria Serena Camassa, Antonella Zumbo, Mariachiara Minerva, Raffaella Iantomasi, Flavio De Maio, Alessandro Cascioferro, Saber Anoosheh, Giorgio Palù, Michael J. Brennan, Riccardo Manganelli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

33 Citazioni (Scopus)

Abstract

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 (MtbA33) 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-PGRS33did 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 MtbA33 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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaPLoS One
Volume11
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Agricultural and Biological Sciences (all)
  • Animals
  • Bacterial Proteins
  • Biochemistry, Genetics and Molecular Biology (all)
  • Cell Line
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis
  • Toll-Like Receptor 2

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