The macrophage mannose receptor (MR) along with complement receptors mediates phagocytosis of the M. tuberculosis virulent strains Erdman and H37Rv. We have determined that the terminal mannosyl units of the M. tuberculosis surface lipoglycan, lipoarabinomannan (LAM), from the Erdman strain serve as ligands for the MR. The biology of the MR (receptor binding and trafficking) in response to phag...

Lymphangioleiomyomatosis (LAM) is a rare disease that affects young women of child-bearing age. It is characterized by the presence of cystic changes in the pulmonary parenchyma, repeated pneumothorax, chylothorax and renal angiomyolipomas, and in the majority of cases it is accompanied by a progressive loss in lung function.1 In the last two decades, there has been an increase in the understan...

Mycobacterium tuberculosis cell wall glycolipid, lipoarabinomannan, can inhibit CD4(+) T cell activation by downregulating the phosphorylation of key proximal TCR signaling molecules: Lck, CD3ζ, ZAP70, and LAT. Inhibition of proximal TCR signaling can result in T cell anergy, in which T cells are inactivated following an Ag encounter, yet remain viable and hyporesponsive. We tested whether mann...

L ymphangioleiomyomatosis (LAM), a slowly progressive disease affecting mostly young and middle-aged females [1], is one of the few orphan lung diseases that has attracted major attention in recent years from both clinicians and researchers [2], with rapidly evolving progress. With an estimated prevalence of one in 400,000 adult females aged 20–69 yrs for the sporadic form [3] and ,30% of patie...

Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease of women. LAM is caused by mutations in the tuberous sclerosis genes, resulting in activation of the mTOR complex 1 signaling network. Over the past 11 years, there has been remarkable progress in the understanding of LAM and rapid translation of this knowledge to an effective therapy. LAM pathogenic mechanisms mirror those of ma...

We sought to determine if urine lipoarabinomannan (LAM) would improve diagnosis of pulmonary TB. We enrolled consecutive adults presenting with ≥2 TB-related symptoms, obtained one induced sputum sample for smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing (Determine(TM) TB LAM, Alere). We used culture-confirmed pulmonary TB as the gold standard, and compared acc...

CD14 is a pattern recognition receptor involved in the interaction with multiple ligands, including LPS from gram-negative bacteria and lipoarabinomannan (LAM) from mycobacteria. While the interactions between LPS and soluble CD14 (sCD14) have been analyzed in detail, LAM/CD14 interactions remain uncharacterized due to the lack of suitable functional assays. We describe herein a novel bioassay ...

BACKGROUND Up to one third of HIV-infected individuals with suspected TB are sputum-scarce. The Alere Determine™ TB LAM Ag lateral flow strip test can be used to diagnose TB in HIV-infected patients with advanced immunosuppression. However, how urine LAM testing should be incorporated into testing algorithms and in the context of specific patient sub-groups remains unclear. METHODS This study...

BACKGROUND Rapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two-sample strategy. METHODS HIV-infected adults eligible for antiretroviral therapy were prospectively enrolled from Korle-Bu Teaching Hospital in Ghana and ...