Advances in Host-Directed Therapies Against Tuberculosis

by Petros C. Karakousis (Editor), Richard Hafner (Editor), Maria Laura Gennaro (Editor)

Overview

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.

Product Details

ISBN-13:	9783030569075
Publisher:	Springer International Publishing
Publication date:	12/04/2020
Edition description:	1st ed. 2021
Pages:	332
Product dimensions:	6.10(w) x 9.25(h) x (d)

About the Author

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.

Table of Contents

Section 1: Introduction

Chapter 1: Introduction: An overview of host-directed therapies for tuberculosis

Daniel Frank, Robert Mahon

Section 2: Targeting immunometabolism

Chapter 2: Sirtuin deacetylases: Linking Mycobacterial infection and host metabolism

Lorissa Smulan, Hardy Kornfeld, and Amit Singhal

Chapter 3: The mammalian target of rapamycin complex 1 (mTORC1): an ally of M. tuberculosis in host cells

Natalie Bruiners, Valentina Guerrini, Maria Laura Gennaro

Chapter 4: HIF-1α as a potential therapeutic target for tuberculosis treatment

Qingkui Jiang, Maria Laura Gennaro, Lanbo Shi

Chapter 5: Nuclear receptors in host-directed therapies against tuberculosis

Eun-Kyeong Jo

Section 3: Enhancing anti-mycobacterial mechanisms

Chapter 6: Autophagy as a target for host-directed therapy against tuberculosis

Surbhi Verma, Raman Deep Sharma and Dhiraj Kumar

Chapter 7: Metformin: a leading HDT candidate for TB

Amit Singhal and Hardy Kornfeld

Chapter 8: Statins as host-directed therapy for tuberculosis

Noton K. Dutta, Petros C. Karakousis

Chapter 9: Antimycobacterial attributes of mihondria: An insight into host defense mechanisms

Rikesh K Dubey, Apoorva Narain

Section 4: Targeting immune cells

Chapter 10: Conventional and unconventional lymphocytes in immunity against Mycobacterium tuberculosis

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

Chapter 11: Targeting inhibitory cells such as Tregs and MDSCs in the tuberculous granuloma

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

Chapter 12: Targeting suppressor T cells

Léanie Kleynhans, Gerhard Walzl

Chapter 13: Neutrophil-mediated mechanisms as targets for host-directed therapies against tuberculosis

Tobias Dallenga, Ulrich E. Schaible

Chapter 14: Type I interferon and interleukin-1 driven inflammatory pathways as targets for HDT in tuberculosis

Katrin D. Mayer-Barber, Christopher M. Sassetti

Chapter 15: Mucosal-associated invariant and Vγ9Vδ2 T cells

Charles K. Vorkas, Michael S. Glickman

Chapter 16: Airway epithelial cells

Angélica M. Olmo-Fontánez, Jordi B. Torrelles

Section 5: Preclinical models for assessing HDTs

Chapter 17: In vitro models of human granuloma formation to analyze host-directed therapies

Liku B. Tezera, Michaela T. Reichmann, Basim Al Shammari, Paul T. Elkington

Chapter 18: C3HeB/FeJ as a key mouse strain for testing host-directed therapies against tuberculosis

Pere-Joan Cardona, Cristina Vilaplana

Chapter 19: The Rabbit Model for Assessing Host-Directed Therapies for Tuberculosis

Selvakumar Subbian, Gilla Kaplan

Section 6: Clinical trials of HDTs and special considerations for study endpoints

Chapter 20: Clinical trials of TB-HDT candidates

Robert S. Wallis

Chapter 21: Outcomes for clinical trials of host-directed therapies for tuberculosis

Akshay N. Gupte, Sara C. Auld, William N. Checkley, Gregory P. Bisson

Chapter 22: Pharmacological considerations for clinical trials of host-directed therapies for tuberculosis

Elisa H. Ignatius, Kelly E. Dooley

Editorial Reviews

Reviewer: Massoud Mahmoudi, DO, PhD (University of California San Francisco)
Description: This book presents up-to-date information on host-directed therapies (HDTs) against tuberculosis. Various mechanisms of such targeted therapy and advances in treatment are nicely described.
Purpose: The purpose is to relay information on advances in therapy against tuberculosis. In addition, the book aims to introduce the ongoing clinical trials to further complement this informative collection.
Audience: The book targets several groups of audiences. The infectious disease specialists who treat tuberculosis are the primary target groups. Other specialists with interest in infection and immunity, infectious disease fellows-in-training, clinical immunologists, and academic pharmacologists will also find this collection resourceful.
Features: This is a medium book of approximately 300 pages. It has 22 chapters divided into six parts: introduction, targeting immunometabolism, enhancing anti-mycobacterial mechanisms, targeting immune cells, preclinical models for assessing HDTs, and clinical trials of HDTs and special considerations. As far as format, the book does not list the name and affiliations of the contributors after the preface section. The chapters are short with limited visual aids. Some chapters end with conclusions while others do not. The number of cited references varies from 29 to 309. This book has no index. I found chapter 1 ("Introduction: An Overview of Host Directed Therapies for Tuberculosis") especially informative since it describes the purpose and history of the host-directed therapy. Another noteworthy part of the book is chapter 20 ("Clinical Trials of TB-HDT Candidates"), which lists the ongoing clinical trials.
Assessment: This is a concise review of advances in host-directed therapies against tuberculosis. The book covers various mechanisms of such therapy and presents information on the ongoing clinical trials. With over 40 contributors, this short review is an informative collection targeting infectious disease specialists who treat tuberculosis and those with interest in the fields of infection and immunity, clinical immunology, and pharmacology.

Doody's Review Service