Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice. Issue 1 (31st October 2013)

• Record Type: Journal Article
• Authors: Santos, José Carlos; Silva‐Gomes, Sandro; Silva, João Pedro; Gama, Miguel; Rosa, Gustavo; Gallo, Richard L.; Appelberg, Rui
• Is Part Of: Immunity, inflammation and disease. Volume 2:Issue 1 (2014)
• Page Start: 1
• Page End: 12
• Publication Date: 2013-10-31
• Subjects: Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.7
• Languages: English
• ISSNs: 2050-4527

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="iid37-sec-0001" sec-type="section"> <p>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 (<italic>Camp</italic>) expression was induced in bone marrow‐derived macrophages by infection with <italic>Mycobacterium avium</italic> 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 <italic>M. avium</italic> either in primary cultures of macrophages or <italic>in vivo</italic>, as shown by the use of CRAMP‐null mice. In contrast, the lack of <italic>Camp</italic> led to a transient improvement of <italic>M. avium</italic> 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.</p> </sec> </abstract>