Cathelicidin is involved in the intracellular killing of mycobacteria in macrophages

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Avinash Sonawane (Author) Other; Jose Carlos Santos (Author) Other; Bibhuti B Mishra (Author) Other; Prajna Jena (Author) Other; Cinzia Progida (Author) Other; Ole E Sorensen (Author) Other; Richard Gallo (Author) Other; Rui Appelberg (Author) ICBAS; Gareth Griffiths (Author) Other

Journal

Title: Cellular Microbiology

Vol. 13

Pages: 1601-1617

ISSN: 1462-5814

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 45 Citations

Scopus - 45 Citations

Pubmed / Medline

Scientific classification

FOS: Natural sciences > Biological sciences

CORDIS: Health sciences > Medical sciences > Medicine

Other information

Authenticus ID: P-002-MA8

DOI: 10.1111/j.1462-5822.2011.01644.x

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17