Reflections on the immunology of tuberculosis: will we ever unravel the skein?

Abstract

Many and large dumps exist in our knowledge about Mycobacterium tuberculosis infection and disease in infants and children. We still do not understand why some individuals do acquire and others do not acquire the infection in the presence of the same risk factors. We do not understand why some individuals convert from latent to active tuberculosis and why other individuals convert from active to inactive tuberculosis even without treatment.As a matter of fact the immune system mounts a bouncing, robust and polyedral defence against Mycobacterium tuberculosis, but the bacillus is so much artful and dextrous that it has ahead from this immunological fierce accoutrements. Mycobacterium tuberculosis survival, multiplication, and transmission are largely favoured by the immune mechanisms. The granuloma itself is more bacillus- than host-protective.These abilities make Mycobacterium tuberculosis one of more successful human pathogens, but dumps in our knowledge and the counterproductive immunity hinder development of new diagnostics, therapies and vaccines. This occurs in front of an infection which engages one third of the world population and a disease which kills in a year about 1.5 million individuals worldwide.Understanding mechanisms and meaning of immune response in tuberculosis marks out the foundations of strategies with a view to prepare effective vaccines and reliable diagnostic tools as well as to build up therapeutic weapons. To gain these objectives is vital and urgent considering that tuberculosis is a common cause of morbidity and is a leading cause of death.

Tuberculosis: A disease without boundaries

“…de Martino et al [7] describe the initial combat of TB once it invades the host using the quote: "All is decided the first day, which gets the longest day". Once the bacterium M. tuberculosis (MTB) is inhaled via droplets spread through person-to-person contact, macrophages can phagocytose and kill the bacilli.…”

“…However, if the bacilli are not killed, during that initial interaction, they can proliferate within dendritic cells and alveolar macrophages at a rapid rate, signaling the production of IL-1-a, IL-1b, and other host proinflammatory cytokines. This response is mediated by pattern recognition receptors (PRRs) [7,11] expressed by macrophages and dendritic cells that recognize pathogen-associated molecular patterns (PAMPS) expressed on MTB [11]. Toll-like receptors (TLRs) help uptake MTB, which induces an intracellular signaling cascade to produce the cytokines.…”

“…Unfortunately, more recent data is not available due to the limits of global surveillance and reporting systems [8]. Additionally, there still remains an incomplete understanding how one person can acquire the disease while another doesn't, though they are exposed to the same risk factors, or how to better determine latent to active TB progression [5,7].…”

“…Additionally, foreign-born individuals and those who reside in impoverished areas or where malnutrition is prevalent are more likely to get infected [2]. The host's own deficiency in interleukin (IL)-12 promoting the T helper (Th) 1 response may be another factor in the increased susceptibility to infection [7]. There are other conditions that may pose a high-risk for susceptibility to MTB infection such as diabetes, ageing, long-term use of corticosteroids, TNF-a blockers, polymorphism in vitamin D receptors, polymorphism in IL-12 and IFN-g genes.…”

Disseminated Mycobacterium chelonae infection in a patient with T-cell lymphoma

“…Most research has been conducted in the host defense against M. tuberculosis, which shows a prominent role for interleukin-12 (IL-12), interferon-c (IFN-c), and tumor necrosis factor-a. These cytokines are responsible for promoting a Type 1 T helper cell (Th-1) response, activating antigen presentation, and phagocytosis [10]. CCR4 is normally associated with a Th-2 immune response, although recent research showed a comparable Th-1 and Th-2 granulomatous response after the introduction of Mycobacterium bovis antigen-coated agarose beads in the lungs of mice.…”