Advances in Host-Directed Therapies Against Tuberculosis

1. Front Matter

   Pages i-xiii

   PDF

2. Introduction

   1. Front Matter

      Pages 1-1

      PDF

   2. Introduction: An Overview of Host-Directed Therapies for Tuberculosis

      • Daniel J. Frank, Robert N. Mahon

      Pages 3-12

3. Targeting Immunometabolism

   1. Front Matter

      Pages 13-13

      PDF

   2. Sirtuin Deacetylases: Linking Mycobacterial Infection and Host Metabolism

      • Lorissa Smulan, Hardy Kornfeld, Amit Singhal

      Pages 15-26

   3. The Mammalian Target of Rapamycin Complex 1 (mTORC1): An Ally of M. tuberculosis in Host Cells

      • Natalie Bruiners, Valentina Guerrini, Maria Laura Gennaro

      Pages 27-40

   4. HIF-1α as a Potential Therapeutic Target for Tuberculosis Treatment

      • Qingkui Jiang, Maria Laura Gennaro, Lanbo Shi

      Pages 41-59

   5. Nuclear Receptors in Host-Directed Therapies against Tuberculosis

      • Eun-Kyeong Jo

      Pages 61-67

4. Enhancing Anti-mycobacterial Mechanisms

   1. Front Matter

      Pages 69-69

      PDF

   2. Autophagy as a Target for Host-Directed Therapy Against Tuberculosis

      • Surbhi Verma, Raman Deep Sharma, Dhiraj Kumar

      Pages 71-95

   3. Metformin: A Leading HDT Candidate for TB

      • Amit Singhal, Hardy Kornfeld

      Pages 97-108

   4. Statins as Host-Directed Therapy for Tuberculosis

      • Noton K. Dutta, Petros C. Karakousis

      Pages 109-119

   5. Antimycobacterial Attributes of Mitochondria: An Insight into Host Defense Mechanisms

      • Rikesh K. Dubey, Apoorva Narain

      Pages 121-129

5. Targeting Immune Cells

   1. Front Matter

      Pages 131-131

      PDF

   2. Conventional and Unconventional Lymphocytes in Immunity Against Mycobacterium tuberculosis

      • Paula Ruibal, Tom H. M. Ottenhoff, Simone A. Joosten

      Pages 133-168

   3. Targeting Inhibitory Cells Such as Tregs and MDSCs in the Tuberculous Granuloma

      • Sadiya Parveen, John R. Murphy, William R. Bishai

      Pages 169-203

   4. Targeting Suppressor T Cells

      • Léanie Kleynhans, Gerhard Walzl

      Pages 205-210

   5. Neutrophil-Mediated Mechanisms as Targets for Host-Directed Therapies Against Tuberculosis

      • Tobias K. Dallenga, Ulrich E. Schaible

      Pages 211-217

   6. Type I Interferon and Interleukin-1 Driven Inflammatory Pathways as Targets for HDT in Tuberculosis

      • Katrin D. Mayer-Barber, Christopher M. Sassetti

      Pages 219-232

   7. H. Mucosal-Associated Invariant and Vγ9Vδ2 T Cells

      • Charles Kyriakos Vorkas, Michael Stephen Glickman

      Pages 233-245

This book discusses specific immune cell regulatory  pathway(s), immune cell types,  or other mechanisms involved in host responses to tuberculosis that can be potentially targeted for host-directed therapy (HDT). The pathways/mechanisms investigated are either protective – thus calling for pathway/factor enhancing drugs – or maladaptive – thus calling for pathway/factor inhibitory drugs. Discovery and development (pre-clinical and clinical) of candidate HDT agents will also be elucidated, as well as approaches for HDT of other diseases. The benefit to the reader will derive from learning about the biology of multiple host pathways involved in health and disease, how these pathways are disrupted or dysregulated during tuberculosis, and which druggable targets exist in these pathways. This book provides the reader with a roadmap of current and future directions of HDT against tuberculosis. Since the host pathways/factors involved in protective or maladaptive responses to tuberculosis are not disease-specific, information learned from the context of tuberculosis likely will be relevant to other infectious and non-infectious diseases.

• host-directed therapy
• immunometabolism
• tuberculosis
• immunopathogenesis
• immune pathways
• inflammation
• infectious diseases
• pharmacotherapy

• Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, USA

  Petros C. Karakousis

• Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, Rockville, USA

  Richard Hafner

• Public Health Research Institute New Jersey Medical School Rutgers Biomedical and Health Sciences, Rutgers-The State University of New Jersey, Newark, USA

  Maria Laura Gennaro

Petros C. Karakousis, M.D., is an infectious diseases-trained physician scientist and Professor of Medicine at the Johns Hopkins University School of Medicine. His research focus is on host-pathogen interactions contributing to Mycobacterium tuberculosis persistence and antibiotic tolerance. His laboratory is actively investigating the repurposing of clinically available agents with immune-modulatory properties as adjunctive host-directed therapy, in order to shorten the duration of TB treatment and improve lung pathology.

Maria Laura Gennaro, M.D., is Professor of Medicine at Rutgers New Jersey School of Medicine. Her laboratory studies mechanisms of adaptation expressed by Mycobacterium tuberculosis and by the host macrophage during infection, with the goal of finding targets for therapeutic intervention. She has a specific interest in macrophage lipid metabolism, which is altered following M. tuberculosis infection, thereby promoting bacterial survival.

Richard Hafner, M.D., is an infectious diseases-trained physician and Chief of the TB Clinical Research Branch in the Division of AIDS at NIAID/NIH. Throughout his career, he has had a long-standing interest in advancing innovative host-directed therapies for infections. He has been involved in several clinical trials, authored various articles, and hosted multiple scientific meetings related to research to develop targeted HDTs for TB.

Policies and ethics