title: Efficacy of gene-therapy based on adenovirus encoding granulocyte-macrophage colony-stimulating factor in drug-sensitive and drug-resistant experimental pulmonary tuberculosis.
abstract: Tuberculosis (TB), although a curable disease, remains a major cause of morbidity and mortality worldwide. It is necessary to develop a short-term therapy with reduced drug toxicity in order to improve adherence rate and control disease burden. Granulocyte-macrophage colony-stimulating factor (GM-CSF) may be a key cytokine in the treatment of pulmonary TB since it primes the activation and differentiation of myeloid and non-myeloid precursor cells, inducing the release of protective Th1 cytokines. In this work, we administrated by intratracheal route recombinant adenoviruses encoding GM-CSF (AdGM-CSF). This treatment produced significant bacterial elimination when administered in a single dose at 60 days of infection with drug sensitive or drug resistant Mtb strains in a murine model of progressive disease. Moreover, AdGM-CSF combined with primary antibiotics produced more rapid elimination of pulmonary bacterial burdens than conventional chemotherapy suggesting that this form of treatment could shorten the conventional treatment.
authors.affiliation: Department of Pathology, National Institute of Medical Sciences and Nutrition 'Salvador Zubirán', Mexico City, Mexico; Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Francisco-Cruz
authors.affiliation: Department of Pathology, National Institute of Medical Sciences and Nutrition 'Salvador Zubirán', Mexico City, Mexico.
authors.forename: Dulce
authors.initials: D
authors.lastname: Mata-Espinosa
authors.affiliation: Department of Pathology, National Institute of Medical Sciences and Nutrition 'Salvador Zubirán', Mexico City, Mexico.
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramos-Espinosa
authors.affiliation: Department of Pathology, National Institute of Medical Sciences and Nutrition 'Salvador Zubirán', Mexico City, Mexico.
authors.forename: Brenda
authors.initials: B
authors.lastname: Marquina-Castillo
authors.affiliation: Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada-Parra
authors.affiliation: McMaster Immunology Research Centre & Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Department of Pathology, National Institute of Medical Sciences and Nutrition 'Salvador Zubirán', Mexico City, Mexico. Electronic address: rhdezpando@hotmail.com.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D015169:Colony Count, Microbial; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000254:growth & development; D012333:RNA, Messenger / Q000235:genetics; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000628:therapy*
chemical_list: D000904:Antibiotics, Antitubercular; D016207:Cytokines; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Adjunct treatment; Granulocyte-macrophage colony-stimulating factor; Multidrug-resistant tuberculosis; Tuberculosis