Cathelicidin is involved in the intracellular killing of mycobacteria in macrophages: The role of cathelicidin in mycobacteria killing
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.
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Part of the anti-mycobacterial activity of cathelicidin is traced to augmentation of NOX2-mediated ROI formation and modulation of cytokine expression.
“Part of the anti-mycobacterial activity of cathelicidin can be traced back to augmentation of NOX2-mediated ROI formation and modulation of cytokine expression (84)”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [84]
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- Authors
- Sonawane, A., Santos, J. C., Mishra, B. B., Jena, P., Progida, C., Sorensen, O. E., Gallo, R., Appelberg, R., & Griffiths, G.
- Affiliations
- KIIT University (IN)
- Universidade do Porto (PT)
- University of Massachusetts Chan Medical School (US)
- University of Oslo (NO)
- University of California San Diego (US)
- ORCID
- Venue
- Cellular Microbiology
- Publisher
- Wiley
- Published
- 2011-08-11
- Volume
- 13
- Issue
- 10
- Pages
- 1601-1617
- ISSN
- 1462-5814 (ISSN-L)
- OpenAlex
- W2117763028
- Cited by
- 165
- References
- 46
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 8 · 2023: 6 · 2022: 11 · 2021: 6 · 2020: 11 · 2019: 16 · 2018: 10 · 2017: 11 · 2016: 13 · 2015: 11 · 2014: 15 · 2013: 15 · 2012: 11
- FWCI
- 12.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- cathelicidin, LL-37, antimicrobial peptides, Mycobacterium tuberculosis, Mycobacterium smegmatis, Mycobacterium bovis BCG, macrophage-mediated killing, 1,25-dihydroxyvitamin D3, phagosome-lysosome fusion, FSL-1, J774 macrophages, peptide variants
- MeSH terms
- Animals, Biological Products, Cells, Cultured, Humans, Macrophages, Mycobacterium bovis, Recombinant Proteins, Gene Expression, Mice, Knockout, Mycobacterium smegmatis, Gene Expression Profiling, Antimicrobial Cationic Peptides, Microbial Viability, Mice, Cathelicidins
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