Understanding The Host Immune Response Against Mycobacterium Tuberculosis Infection

According to the World Health Organization, approximately one third of the world’s population is latently infected with Mycobacterium tuberculosis (M. tb [LTBI]), of whom about 9 million have active tuberculosis (TB). It is estimated that approximately 2 million individuals die each year from active TB. An estimated 14.4% of these individuals have HIV and M. tb co-infection. TB has long been known to be one of the leading causes of death in HIV-infected individuals. Recent evidence now indicates that individuals with type 2 diabetes, the elderly, and chronic smokers are also increasingly susceptible to TB infection, the ability of their immune system to fight off active TB infection having been compromised by their condition. This book therefore aims to provide a detailed review of recent advances in the research that involves characterizing the host’s immune responses against TB infection in conditions such as HIV, diabetes, chronic cigarette smoking and aging, and strategies to restore favorable immune responses against this deadly pathogen.

This book illustrates the intimate relationship between alveolar macrophages and Mycobacterium tuberculosis (M.tb.), and the former’s role in both innate and adaptive immunity against M.tb. It covers research done over the last decade. It also explores the role of macrophage death following infection with M.tb. in determining whether successful immunity is stimulated, or whether clinical disease develops; furthermore, the function of host lipid mediators in macrophage death modality are addressed. The book also illustrates how the balance between prostaglandins and lipoxins determines whether infected macrophages undergo apoptosis or necrosis, which is the ultimate factor in the outcome of infection. Finally, it is a synthesis of the authors’ recent studies and the studies of others to offer a new understanding of immunity to tuberculosis.

This book summarizes the progress in studies of tuberculosis host-pathogen interactions from several perspectives: molecular microbiology, immunology, animal models, clinical studies, epidemiology, and drug discovery. Tuberculosis (TB) remains a severe global public health problem. Complex interactions between environmental, microbial and host factors lead to clinically relevant infections. Studies on bacterial virulence, host-genetic, and immunological factors contributing to the susceptibility to TB provide an ever-growing foundation of knowledge that is critical to finding new interventions. Studies of immune mechanisms against M. tuberculosis infection have identified immunological markers associated with specific phenotypes in the host, providing insight into how they may be used to augment current treatment strategies. Recent advances in diagnosis, therapeutics and vaccines, as well as basic-research oriented studies have shed light on the development of new directions for prevention, treatment and control of TB. Improved understanding of the interplay between the bacterium and host is a key component of reducing incidence worldwide.

Mycobacterium tuberculosis in an attempt to understand the extent to which the bacilli has adapted itself to the host and to its final target. On the other hand, there is a section in which other specialists discuss how to manipulate this immune response to obtain innovative prophylactic and therapeutic approaches to truncate the intimal co-evolution between Mycobacterium tuberculosis and the Homo sapiens.

Can today's innovative practices and molecular tools tame this ancient disease? One third of the world's population is infected with tuberculosis (TB), with about 10 million new cases annually. To combat TB and its agent, Mycobacterium tuberculosis, the World Health Organization launched The End TB Strategy, which aims to slash the suffering and cost of TB by 2035. This makes the second edition of Tuberculosis and the Tubercle Bacillus, edited by Jacobs, McShane, Mizrahi, and Orme, an extremely valuable resource for scientists and clinicians. The editors have gathered their colleagues from around the world to present the latest on the molecular biology of M. tuberculosis and related species, the host-pathogen interactions that enable invasion, and the host's immune response to M. tuberculosis infection. The basic, clinical, and translational research presented in this book supports the goals of WHO's End TB Strategy by driving toward the development of effective vaccines, rapid molecular diagnostics, and anti-TB drugs. Creating an effective tuberculosis vaccine. Understand the innate and adaptive immune response to M. tuberculosis infection, its study in established animal models, and how this information is being used to develop new vaccines against TB. Formulating new antituberculosis drugs. Learn the challenges and methods for evaluating new drugs in preclinical trials with a focus on drugs that work against "persisters" and those that act on the electron transport complex and ATP synthase of M. tuberculosis. Overcoming the challenges of diagnosing tuberculosis. Review new diagnostic tools that are simple, rapid, affordable, specific, sensitive, and safe, including molecular-based diagnostic methods such as GeneXpert MTB/RIF. Using molecular, genomic, and bioinformatics tools to understand the biology and evolution of Mycobacterium. Explore current research on the molecular mechanisms that M. tuberculosis uses to evade the immune system, enter a state of nonreplicating persistence, and become reactivated. The second edition of Tuberculosis and the Tubercle Bacillus presents the latest research on a microorganism that is exquisitely well adapted to its human host. This pathogen continues to confound scientists, clinicians, and public health specialists, who will all find much valuable information in this comprehensive set of reviews.

TB is considered as one of the oldest documented infectious diseases in the world and is believed to be the leading cause of mortality due to a single infectious agent. Mtb, the causative agent responsible for TB, continues to afflict millions of people worldwide. Furthermore, one-third of the entire world's population has latent TB. Consequently, there has been a worldwide effort to eradicate and limit the spread of Mtb through the use of antibiotics. However, management of TB is becoming more challenging with the emergence of drug-resistant and multi-drug resistant strains of Mtb. Furthermore, when administered, many of the anti-TB drugs commonly present severe complications and side effects. Novel approaches to enhance the host immune responses to completely eradicate Mtb infection are urgently needed. This Special Issue will therefore cover most recent advances in the area of host-directed therapies for TB.