Enhancement of CD4+ T Cell Function as a Strategy for Improving Antibiotic Therapy Efficacy in Tuberculosis: Does It Work?

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.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States.
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.
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.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States.

Resumo em Inglês

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.

Palavras-chave

Tuberculose
Mycobacterium tuberculosis
Terapêutica
Imunização
Linfócitos T
Interleucina-12

Palavras-chave em inglês

Tuberculosis
Host-directed therapy
Adaptive immunity
CD4+ T lymphocytes
IFN-g
TNF
IL-12

Editor

Frontiers Media

Referência

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.

DOI

10.3389/fcimb.2021.672527

ISSN

2235-2988

Use este identificador para citar ou linkar para este item: https://www.arca.fiocruz.br/handle/icict/48038

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Direito Autoral

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