Cathelicidin is involved in the intracellular killing of mycobacteria in macrophages.
(2011) In Cellular Microbiology 13. p.1601-1617- 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... (More)
- 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 knock-down 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2151771
- author
- Sonawane, Avinash ; Santos, Jose Carlos ; Mishra, Bibhuti B ; Jena, Prajna ; Progida, Cinzia ; Sørensen, Ole E LU ; Gallo, Richard ; Appelberg, Rui and Griffiths, Gareth
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cellular Microbiology
- volume
- 13
- pages
- 1601 - 1617
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000294924500013
- pmid:21790937
- scopus:80052794411
- pmid:21790937
- ISSN
- 1462-5814
- DOI
- 10.1111/j.1462-5822.2011.01644.x
- language
- English
- LU publication?
- yes
- id
- d8afdb68-453b-4c94-8106-910ecbc5cc0f (old id 2151771)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21790937?dopt=Abstract
- date added to LUP
- 2016-04-04 08:54:48
- date last changed
- 2022-04-15 21:07:32
@article{d8afdb68-453b-4c94-8106-910ecbc5cc0f,
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 knock-down 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.}},
author = {{Sonawane, Avinash and Santos, Jose Carlos and Mishra, Bibhuti B and Jena, Prajna and Progida, Cinzia and Sørensen, Ole E and Gallo, Richard and Appelberg, Rui and Griffiths, Gareth}},
issn = {{1462-5814}},
language = {{eng}},
pages = {{1601--1617}},
publisher = {{Wiley-Blackwell}},
series = {{Cellular Microbiology}},
title = {{Cathelicidin is involved in the intracellular killing of mycobacteria in macrophages.}},
url = {{http://dx.doi.org/10.1111/j.1462-5822.2011.01644.x}},
doi = {{10.1111/j.1462-5822.2011.01644.x}},
volume = {{13}},
year = {{2011}},
}