| Author | Costa, Diego L. | |
| Author | Amaral, Eduardo P. | |
| Author | Namasivayam, Sivaranjani | |
| Author | Mittereder, Lara R. | |
| Author | Andrade, Bruno de Bezerril | |
| Author | Sher, Alan | |
| Access date | 2021-07-07T16:16:12Z | |
| Available date | 2021-07-07T16:16:12Z | |
| Document date | 2021 | |
| Citation | COSTA, Diego L. et al. Enhancement of CD4+ T Cell Function as a Strategy for Improving Antibiotic Therapy Efficacy in Tuberculosis: Does It Work? Frontiers in Cellular and Infection Microbiology, 2021. | pt_BR |
| ISSN | 2235-2988 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/48038 | |
| Sponsorship | Intramural Research Program of
the NIAID. DC is currently funded by Fundação de Amparo à
Pesquisa do Estado de São Paulo (FAPESP), grant #2019/08445-
8. SN, EA, and AS are funded by the Intramural Research
Program of the NIAID, NIH. BA is funded by the Intramural
Research Program of the Fundação Oswaldo Cruz, Brazil, and is
a senior fellow of the Conselho Nacional de Desenvolvimento
Cientı́fico e Tecnológico, Brazil. | pt_BR |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Tuberculose | pt_BR |
| Subject in Portuguese | Mycobacterium tuberculosis | pt_BR |
| Subject in Portuguese | Terapêutica | pt_BR |
| Subject in Portuguese | Imunização | pt_BR |
| Subject in Portuguese | Linfócitos T | pt_BR |
| Subject in Portuguese | Interleucina-12 | pt_BR |
| Title | Enhancement of CD4+ T Cell Function as a Strategy for Improving Antibiotic Therapy Efficacy in Tuberculosis: Does It Work? | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.3389/fcimb.2021.672527 | |
| Abstract | Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) remains a major public
health problem worldwide due in part to the lack of an effective vaccine and to the lengthy
course of antibiotic treatment required for successful cure. Combined immuno/
chemotherapeutic intervention represents a major strategy for developing more effective
therapies against this important pathogen. Because of the major role of CD4+ T cells in
containing Mtb infection, augmentation of bacterial specific CD4+ T cell responses has
been considered as an approach in achieving this aim. Here we present new data from our
own research aimed at determining whether boosting CD4+ T cell responses can promote
antibiotic clearance. In these studies, we first characterized the impact of antibiotic
treatment of infected mice on Th1 responses to major Mtb antigens and then
performed experiments aimed at sustaining CD4+ T cell responsiveness during
antibiotic treatment. These included IL-12 infusion, immunization with ESAT-6 and
Ag85B immunodominant peptides and adoptive transfer of Th1-polarized CD4+ T cells
specific for ESAT-6 or Ag85B during the initial month of chemotherapy. These
approaches failed to enhance antibiotic clearance of Mtb, indicating that boosting Th1
responses to immunogenic Mtb antigens highly expressed by actively dividing bacteria is
not an effective strategy to be used in the initial phase of antibiotic treatment, perhaps
because replicating organisms are the first to be eliminated by the drugs. These results are
discussed in the context of previously published findings addressing this concept along with possible alternate approaches for harnessing Th1 immunity as an adjunct
to chemotherapy. | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquíımica e Imunologia. Ribeirão Preto, SP, Brasil / Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Ribeirão Preto, SP, Brasil / National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States. | pt_BR |
| Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States. | pt_BR |
| Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States. | pt_BR |
| Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States / Center for Biologics Evaluation and Research, Food and Drug Administration. Laboratory of Mucosal Pathogens and Cellular Immunology. Division of Bacterial, Parasitic and Allergenic Products Silver Spring. MD, United States. | pt_BR |
| Affilliation | University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Curso de Medicina. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, United States. | pt_BR |
| Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States. | pt_BR |
| Subject | Tuberculosis | pt_BR |
| Subject | Host-directed therapy | pt_BR |
| Subject | Adaptive immunity | pt_BR |
| Subject | CD4+ T lymphocytes | pt_BR |
| Subject | IFN-g | pt_BR |
| Subject | TNF | pt_BR |
| Subject | IL-12 | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
