| Author | Costa, Diego Luis | |
| Author | Namasivayam, Sivaranjani | |
| Author | Amaral, Eduardo Pinheiro | |
| Author | Arora, Kriti | |
| Author | Chao, Alex | |
| Author | Mittereder, Lara R | |
| Author | Maiga, Mamoudou | |
| Author | Boshoff, Helena I | |
| Author | Barry, Clifton E | |
| Author | Goulding, Celia W | |
| Author | Andrade, Bruno de Bezerril | |
| Author | Sher, Alan | |
| Access date | 2017-03-22T17:57:18Z | |
| Available date | 2017-03-22T17:57:18Z | |
| Document date | 2016 | |
| Citation | COSTA, D. L. et al. Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes. mBio, v. 7, n. 5, p. e01675-16, 2016. | pt_BR |
| ISSN | 2150-7511 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/18119 | |
| Sponsorship | Brazilian National Council of Scientific and Technological Development (CNPq) (237267/2012-8). National Institutes of Health (NIH) (AI095208). NIH National Institute of Allergy and Infectious Diseases
(NIAID) (Intramural Research Program). National Science Foundation (NSF) (NSF-GRFP DGE-1321846). | pt_BR |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Mycobacterium tuberculosis | pt_BR |
| Subject in Portuguese | Heme oxigenase | pt_BR |
| Subject in Portuguese | Infecção | pt_BR |
| Subject in Portuguese | Humanos | pt_BR |
| Subject in Portuguese | Antibióticos | pt_BR |
| Subject in Portuguese | Tuberculose | pt_BR |
| Title | Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1128/mBio.01675-16 | |
| Abstract | Heme oxygenase-1 (HO-1) is a stress response antioxidant enzyme which catalyzes the degradation of heme released during inflammation. HO-1 expression is upregulated in both experimental and human Mycobacterium tuberculosis infection, and in patients it is a biomarker of active disease. Whether the enzyme plays a protective versus pathogenic role in tuberculosis has been the subject of debate. To address this controversy, we administered tin protoporphyrin IX (SnPPIX), a well-characterized HO-1 enzymatic inhibitor, to mice during acute M. tuberculosis infection. These SnPPIX-treated animals displayed a substantial reduction in pulmonary bacterial loads comparable to that achieved following conventional antibiotic therapy. Moreover, when administered adjunctively with antimycobacterial drugs, the HO-1 inhibitor markedly enhanced and accelerated pathogen clearance. Interestingly, both the pulmonary induction of HO-1 expression and the efficacy of SnPPIX treatment in reducing bacterial burden were dependent on the presence of host T lymphocytes. Although M. tuberculosis expresses its own heme-degrading enzyme, SnPPIX failed to inhibit its enzymatic activity or significantly restrict bacterial growth in liquid culture. Together, the above findings reveal mammalian HO-1 as a potential target for host-directed monotherapy and adjunctive therapy of tuberculosis and identify the immune response as a critical regulator of this function. | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Clinical Infectious Diseases. Tuberculosis Research Section. Bethesda, MD, USA | pt_BR |
| Affilliation | University of California. Department of Pharmaceutical Sciences. Irvine, CA, USA | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Clinical Infectious Diseases. Tuberculosis Research Section. Bethesda, MD, USA | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Clinical Infectious Diseases. Tuberculosis Research Section. Bethesda, MD, USA | pt_BR |
| Affilliation | University of California. Department of Molecular Biology and Biochemistry. Irvine, CA, USA / University of California. Departmente of Pharmaceutical Sciences. Irvine, CA, USA | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA / Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz. Unidade de Medicina Investigativa. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para a Investigação da Tuberculose. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil | pt_BR |
| Affilliation | NIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
| Subject | Mycobacterium tuberculosis | pt_BR |
| Subject | Heme oxygenase | pt_BR |
| Subject | Infection | pt_BR |
| Subject | Humans | pt_BR |
| Subject | Antibiotic | pt_BR |
| Subject | Tuberculosis | pt_BR |
