Main description:

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.

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-1 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 mitochondria: 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

Leanie 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 V 9V 2 T cells

Charles K. Vorkas, Michael S. Glickman

Chapter 16: Airway epithelial cells

Angelica M. Olmo-Fontanez, 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