title: Induction of β-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis.
abstract: 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.
authors.affiliation: Experimental Pathology Section, National Institute of Medical Sciences and Nutrition, Mexico City, Mexico.
authors.forename: C E
authors.initials: CE
authors.lastname: Rivas-Santiago
authors.forename: B
authors.initials: B
authors.lastname: Rivas-Santiago
authors.forename: D A
authors.initials: DA
authors.lastname: León
authors.forename: J
authors.initials: J
authors.lastname: Castañeda-Delgado
authors.forename: R
authors.initials: R
authors.lastname: Hernández Pando
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D007532:Isoleucine / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C106641:DEFB4A protein, human; C513975:Defb4 protein, mouse; D023083:beta-Defensins; C540070:beta-defensin 3, mouse; D007532:Isoleucine