Abstract
Tuberculosis (TB) is still a severe public health problem; the current diagnostic tests have limitations that delay treatment onset. Lipoarabinomannan (LAM) is a glycolipid that is a component of the cell wall of the bacillus Mycobacterium tuberculosis, the etiologic agent of TB. This glycolipid is excreted as a soluble form in urine. The World Health Organization has established that the design of new TB diagnostic methods is one of the priorities within the EndTB Strategy. LAM has been suggested as a biomarker to develop diagnostic tests based on its identification in urine, and it is one of the most prominent candidates to develop point-of-care diagnostic test because urine samples can be easily collected. Moreover, LAM can regulate the immune response in the host and can be found in the serum of TB patients, where it probably affects a wide variety of host cell populations, consequently influencing the quality of both innate and adaptive immune responses during TB infection. Here, we revised the evidence that supports that LAM could be used as a tool for the development of new point-of-care tests for TB diagnosis, and we discussed the mechanisms that could contribute to the low sensitivity of diagnostic testing.
Highlights
Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb)
As discussed below, LAM has the ability to modulate the host immune response but, interestingly, the induced changes could be different during each infection stage, which could be related to the modifications that LAM suffers during its synthesis
Additional studies have demonstrated the potential of many molecules that may promote the reactivation of cells exposed to LAM, such as high-mobility group box 1 (HMGB1), a danger-associated molecular pattern (DAMP) that can enhance the innate response to Mtb-antigens like LAM (Lui et al, 2016)
Summary
Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). Older men and women represented nearly 88% of all cases (World Health Organization, 2020) Risk factors such as diabetes mellitus, human immunodeficiency virus (HIV) co-infection, malnutrition, smoking, and alcoholism are associated with the development of TB (Glaziou et al, 2018; Melsew et al, 2018). The Mycobacterium cell wall has integrated virulence factors that are upregulated and are helpful in avoiding the host immune response (Bah et al, 2020). Lipoarabinomannan (LAM) is a cell wall glycolipid; its structural core is inserted into the plasma membrane of Mtb. LAM is considered as a potential tool to be used as a biomarker for TB diagnosis. In the specific case of manLAM, it has a terminal cap called “capping motif of LAM”; these terminal residues could be mannose or tetra-/ hex-arabinofuranoside (Figure 2B; Angala et al, 2017; Abrahams and Besra, 2018; Choudhary et al, 2018)
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