Genetics and Immunity of Mycobacterial Infections: A Battle of Two Genomes 2.0

Dear Colleagues,

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is one of the most successful pathogens of mankind, currently infecting one-quarter of the global population and claiming about 1.5 million lives every year. The long adaptive co-evolution of mycobacterial offensive and human defensive mechanisms has resulted in a wide spectrum of TB susceptibility and severity, ranging from asymptomatic latency to progressive fatal disease. The ability of mycobacteria to persist in the immune host in a latent state is often considered central to the host–pathogen relationship. Recent advances in mycobacterial genetics and virulence mechanisms, on the one hand, and host immunity and genetic susceptibility, on the other hand, provide an opportunity for renewed investigation of this major threat to human health. The plethora of mycobacterial disease manifestations and long history of research on TB (and leprosy) have made these infections a “gold standard” for investigating the pathogenesis of chronic infectious diseases and the elucidation of fundamental concepts of parasitism. TB, when viewed as an interaction between two co-evolving species each with their own survival strategies, a “battle of two genomes”, has emerged as a paradigm for intracellular parasitism.

Genetic investigations of TB infection susceptibility and disease severity have been ongoing for decades, both in experimental and clinical settings, but have gained traction recently in functional studies, including the microRNAs, transcriptomics, proteomics and epigenetics of the host and parasite. The previously unappreciated importance of innate host defense mechanisms has revolutionized the understanding of the host–pathogen relationship. Effective adaptive immune responses, including the key activity of mycobacteria-specific and bystander CD4+ and CD8+ effector and regulatory T cell populations, can control mycobacterial populations throughout the body, but can also promote the development of progressively destructive lesions in host tissues. The role of B cells and humoral immunity, long overlooked by mycobacterial researchers, has received renewed interest. Host and parasite genomics are the most powerful aspects when focusing on carefully selected immune/pathology phenotypes in specific host–pathogen combinations. The genetic and physiological manipulation of mycobacteria and the rational selection of genetically defined hosts in experimental settings provide useful information about how mycobacteria alter the innate and acquired immune responses of hosts, and what features of pathology underlie protective vs. pathogenic inflammatory responses. We believe that a series of articles within this framework will make a valuable contribution to a better understanding of these very important, rapidly developing and still highly controversial aspects of mycobacterial research.

Prof. Dr. David N. McMurray
Prof. Dr. Alexander S. Apt
Guest Editors

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• tuberculosis
• mycobacteria-host interactions
• virulence factors
• mycobacteria and host gene expression
• lung inflammation
• TB latency

• Genetics and Immunity of Mycobacterial Infections: A Battle of Two Genomes in International Journal of Molecular Sciences (9 articles)