Article

Antimycobacterial agent based on mRNA encoding human beta-defensin 2 enables primary macrophages to restrict growth of Mycobacterium tuberculosis.

Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Infection and Immunity (impact factor: 4.16). 05/2001; 69(4):2692-9. DOI:10.1128/IAI.69.4.2692-2699.2001 pp.2692-9
Source: PubMed

ABSTRACT Human macrophages are hosts for Mycobacterium tuberculosis, the causative agent of tuberculosis, which killed approximately 1.87 million people in 1997. Human alveolar macrophages do not express alpha- or beta-defensins, broad-spectrum antimicrobial peptides which are expressed in macrophages from other species more resistant to infection with M. tuberculosis. It has been previously reported that M. tuberculosis is susceptible to killing by defensins, which may explain the difference in resistance. Defensin peptides have been suggested as a possible therapeutic strategy for a variety of infectious diseases, but development has been hampered by difficulties in their large-scale production. Here we report the cellular synthesis of human beta-defensin 2 via highly efficient mRNA transfection of human macrophages. This enabled mycobactericidal and mycobacteristatic activity by the macrophages. Although human macrophages are difficult to transfect with plasmid vectors, these studies illustrate that primary macrophages are permissive for mRNA transfection, which enabled expression of a potentially therapeutic protein.

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Keywords

1.87 million people
 
beta-defensins
 
broad-spectrum antimicrobial peptides
 
cellular synthesis
 
efficient mRNA transfection
 
enabled expression
 
enabled mycobactericidal
 
Human alveolar macrophages
 
human beta-defensin 2
 
human macrophages
 
infectious diseases
 
large-scale production
 
M. tuberculosis
 
mRNA transfection
 
Mycobacterium tuberculosis
 
plasmid vectors
 
possible therapeutic strategy
 
primary macrophages
 
resistant
 
therapeutic protein
 

K O Kisich