Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/97101
Author(s): Avinash Sonawane
Jose Carlos Santos
Bibhuti B Mishra
Prajna Jena
Cinzia Progida
Ole E Sorensen
Richard Gallo
Rui Appelberg
Gareth Griffiths
Title: Cathelicidin is involved in the intracellular killing of mycobacteria in macrophages
Issue Date: 2011
Abstract: Macrophages 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.
Subject: Medicina, Ciências biológicas
Medicine, Biological sciences
Scientific areas: Ciências exactas e naturais::Ciências biológicas
Natural sciences::Biological sciences
URI: https://repositorio-aberto.up.pt/handle/10216/97101
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:ICBAS - Artigo em Revista Científica Internacional

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