Induction of β-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis

• Published in: Clinical and experimental immunology Vol. 164; no. 1; pp. 80 - 89
• Main Authors: Rivas-Santiago, CE, Rivas-Santiago, B, Leon, DA, Castaneda-Delgado, J, Hernandez Pando, R
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2011; Blackwell; Blackwell Science Inc
• Subjects: Analytical, structural and metabolic biochemistry; Animal models; Animals; Antimicrobial peptides; anti‐microbial peptides; Bacterial diseases; beta-Defensins - genetics; beta-Defensins - immunology; beta-Defensins - metabolism; Biological and medical sciences; Cell Line, Tumor; Clinical isolates; Cytokines; Defensins; Disease Models, Animal; Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - drug effects; Human bacterial diseases; Humans; Immunohistochemistry; Immunotherapy; Immunotherapy - methods; Infection; Infectious diseases; Isoleucine - administration & dosage; Isoleucine - pharmacology; L-isoleucine; Lung; Lung - drug effects; Lung - immunology; Lung - microbiology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Morphometry; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - immunology; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; therapy; Trachea; Translational Studies; Tuberculosis; Tuberculosis - immunology; Tuberculosis - microbiology; Tuberculosis - therapy; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; Tuberculosis, Pulmonary - therapy; defensins; Peptides; Induction; therapy; Rodentia; Biochemistry; Mycobacterial infection; Experimental study; anti-microbial peptides; Infection; Vertebrata; Mammalia; Treatment; Tuberculosis; Mouse; Aminoacid; Animal; Immunotherapy; Bacteriosis; Defensin; Isoleucine; L-isoleucine
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2010.04313.x

Tuberculosis is a worldwide health problem, and multidrug-resistant (MDR) and extensively multidrug-resistant (XMDR) strains are rapidly emerging and threatening the control of this disease. These problems motivate the search for new treatment strategies. One potential strategy is immunotherapy using cationic anti-microbial peptides. The capacity of l-isoleucine to induce beta-defensin expression and its potential therapeutic efficiency were studied in a mouse model of progressive pulmonary tuberculosis. BALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv or with a MDR clinical isolate by the intratracheal route. After 60 days of infection, when disease was in its progressive phase, mice were treated with 250 µg of intratracheal l-isoleucine every 48 h. Bacillary loads were determined by colony-forming units, protein and cytokine gene expression were determined by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively, and tissue damage was quantified by automated morphometry. Administration of l-isoleucine induced a significant increase of beta-defensins 3 and 4 which was associated with decreased bacillary loads and tissue damage. This was seen in animals infected with the antibiotic-sensitive strain H37Rv and with the MDR clinical isolate. Thus, induction of beta-defensins might be a potential therapy that can aid in the control of this significant infectious disease.