Abstract
The production of antimicrobial peptides, such as the cathelicidins, plays a prominent role in the innate immune response against microbial pathogens. Cathelicidins are widely distributed amongst living organisms, and the antimicrobial peptides generated by proteolysis of the precursor forms are typically cationic and α-helical, a structure that facilitates their interaction and insertion into anionic bacterial cell walls and membranes, causing damage and promoting microbial death. Here, we found that mouse cathelicidin (Camp) expression was induced in bone marrow-derived macrophages by infection with Mycobacterium avium in a TLR2- and TNF-dependent manner. However, the endogenous production of the cathelin-related antimicrobial peptide (CRAMP) was not required for the bacteriostasis of M. avium either in primary cultures of macrophages or in vivo, as shown by the use of CRAMP-null mice. In contrast, the lack of Camp led to a transient improvement of M. avium growth control in the spleens of infected mice while at the same time causing an exacerbation of the inflammatory response to infection. Our data highlight the anti-inflammatory effects of CRAMP and suggests that virulent mycobacteria may possess strategies to escape its antimicrobial activity.
Highlights
Innate immunity provides the first line of defense against infection by pathogenic microorganisms
Infection of BMMf, TLR2/6 activation or treatment with TNF, all led to an increase of Camp mRNA levels
In order to get insights into the mechanism by which M. avium induces cathelicidin expression, we showed that TLR2 or TNF
Summary
Innate immunity provides the first line of defense against infection by pathogenic microorganisms. An important branch of innate immunity is composed by antimicrobial peptides (AMPs), a group of unique and diverse molecules with a wide range of microbicidal activity [1, 2]. Cathelicidins are synthesized as precursors in a pre-pro-peptide form that is first cleaved into a pro-peptide, designated pro-LL-37 or hCAP18 in humans and pro-CRAMP (cathelin-related antimicrobial peptide) in mice, and to the mature bioactive peptide LL-37 or CRAMP, respectively [11, 12] Both LL-37 and CRAMP are amphipathic, a-helical peptides, with a net positive charge of (þ6) [10, 13] that preferentially binds to negatively charged groups of the outer leaflet of the bacterial envelope. This leads to displacement of lipids, alteration of membrane structure and to the creation of a physical pore in the membrane causing bacterial contents to leak out [14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
