Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/97101
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dc.creatorAvinash Sonawane
dc.creatorJose Carlos Santos
dc.creatorBibhuti B Mishra
dc.creatorPrajna Jena
dc.creatorCinzia Progida
dc.creatorOle E Sorensen
dc.creatorRichard Gallo
dc.creatorRui Appelberg
dc.creatorGareth Griffiths
dc.date.accessioned2019-02-02T19:02:39Z-
dc.date.available2019-02-02T19:02:39Z-
dc.date.issued2011
dc.identifier.issn1462-5814
dc.identifier.othersigarra:88486
dc.identifier.urihttps://repositorio-aberto.up.pt/handle/10216/97101-
dc.description.abstractMacrophages have been shown to kill Mycobacterium tuberculosis through the action of the antimicrobial peptide cathelicidin (CAMP), whose expression was shown to be induced by 1,25-dihydroxyvitamin D3 (1,25D3). Here, we investigated in detail the antimycobacterial effect of murine and human cathelicidin against Mycobacterium smegmatis and M. bovis BCG infections. We have synthesized novel LL-37 peptide variants that exhibited potent in vitro bactericidal activity against M. smegmatis, M. bovis BCG and M. tuberculosis H37Rv, as compared with parental peptide. We show that the exogenous addition of LL-37 or endogenous overexpression of cathelicidin in macrophages significantly reduced the intracellular survival of mycobacteria relative to control cells. An upregulation of cathelicidin mRNA expression was observed that correlated with known M. smegmatis killing phases in J774 macrophages. Moreover, RNAi-based Camp knockdown macrophages and Camp(-/-) bone marrow derived mouse macrophages were significantly impaired in their ability to kill mycobacteria. M. smegmatis killing in Camp(-/-) macrophages was less extensive than in Camp(+/+) cells following activation with FSL-1, an inducer of cathelicidin expression. Finally we show that LL-37 and 1,25D3 treatment results in increase in colocalization of BCG-containing phagosomes with lysosomes. Altogether, these data demonstrate that cathelicidin plays an important role in controlling intracellular survival of mycobacteria.
dc.language.isoeng
dc.rightsrestrictedAccess
dc.subjectMedicina, Ciências biológicas
dc.subjectMedicine, Biological sciences
dc.titleCathelicidin is involved in the intracellular killing of mycobacteria in macrophages
dc.typeArtigo em Revista Científica Internacional
dc.contributor.uportoInstituto de Ciências Biomédicas Abel Salazar
dc.identifier.doi10.1111/j.1462-5822.2011.01644.x
dc.identifier.authenticusP-002-MA8
dc.subject.fosCiências exactas e naturais::Ciências biológicas
dc.subject.fosNatural sciences::Biological sciences
Appears in Collections:ICBAS - Artigo em Revista Científica Internacional

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