title: Ability of innate defence regulator peptides IDR-1002, IDR-HH2 and IDR-1018 to protect against Mycobacterium tuberculosis infections in animal models.
abstract: Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15-30 µg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB.
authors.affiliation: Medical Research Unit Zacatecas, Mexican Institute of Social Security-IMSS, Zacatecas, Mexico.
authors.forename: Bruno
authors.initials: B
authors.lastname: Rivas-Santiago
authors.forename: Julio E
authors.initials: JE
authors.lastname: Castañeda-Delgado
authors.forename: Cesar E
authors.initials: CE
authors.lastname: Rivas Santiago
authors.forename: Matt
authors.initials: M
authors.lastname: Waldbrook
authors.forename: Irma
authors.initials: I
authors.lastname: González-Curiel
authors.forename: Juan C
authors.initials: JC
authors.lastname: León-Contreras
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Enciso-Moreno
authors.forename: Victor
authors.initials: V
authors.lastname: del Villar
authors.forename: Jazmin
authors.initials: J
authors.lastname: Mendez-Ramos
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernandez-Pando
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D058491:Bacterial Load / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D056747:Immunomodulation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
chemical_list: D023181:Antimicrobial Cationic Peptides; D000995:Antitubercular Agents; D016207:Cytokines; C549067:IDR 1002; C555052:innate defense regulating peptide 1018
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