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Association of lipoarabinomannan with high density lipoprotein in blood: Implications for diagnostics

Journal Article · · Tuberculosis
 [1];  [1];  [2];  [2];  [3];  [3];  [1];  [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. International Tuberculosis Research Center, Changwon (Republic of Korea)
  3. National Inst. of Allergy and Infectious Diseases, Bethesda, MD (United States)
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Understanding the pathophysiology of tuberculosis, and the bio-distribution of pathogen-associated molecules in the host is essential for the development of efficient methods of intervention. One of the key virulence factors in the pathology of tuberculosis infection is Lipoarabinomannan (LAM). Previously, we have demonstrated the reliable detection of LAM in urine from tuberculosis patients in a sandwich immunoassay format. We also applied an ultra-sensitive detection strategy developed for amphiphilic biomarkers, membrane insertion, to the detection of LAM with a limit of detection of 10 fM. Herein, we evaluate the application of membrane insertion to the detection of LAM in patient serum, and demonstrate that the circulating concentrations of ‘monomeric’ LAM in serum are very low, despite significantly higher concentrations in the urine. Using spiked samples, we demonstrate that this discrepancy is due to the association of LAM with high-density lipoprotein (HDL) nanodiscs in human serum. Indeed, pull-down of HDL nanodiscs from human serum allows for the recovery of HDL-associated LAM. These studies suggest that LAM is likely associated with carrier molecules such as HDL in the blood of patients infected with tuberculosis. Furthermore, this phenomenon may not be limited to LAM in that many pathogen-associated molecular patterns like LAM are amphiphilic in nature and may also be associated with host lipid carriers. Such interactions are likely to affect host–pathogen interactions, pathogen bio-distribution and clearance in the host, and must be thoroughly understood for the effective design of vaccines and diagnostics.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1235738
Report Number(s):
LA-UR--14-28713; PII: S1472979213000383
Journal Information:
Tuberculosis, Journal Name: Tuberculosis Journal Issue: 3 Vol. 93; ISSN 1472-9792
Country of Publication:
United States
Language:
English

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Cited By (13)

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Exposure of Monocytes to Lipoarabinomannan Promotes Their Differentiation into Functionally and Phenotypically Immature Macrophages journal January 2015
Biomarkers for tuberculosis: the case for lipoarabinomannan journal February 2019
Mannosylated lipoarabinomannan in serum as a biomarker candidate for subclinical bovine tuberculosis journal August 2014
Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment journal January 2019
Membrane Insertion for the Detection of Lipopolysaccharides: Exploring the Dynamics of Amphiphile-in-Lipid Assays journal May 2016
Lipoarabinomannan Decreases Galectin-9 Expression and Tumor Necrosis Factor Pathway in Macrophages Favoring Mycobacterium tuberculosis Intracellular Growth journal November 2017
Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics journal July 2017
Understanding the Significance of Biochemistry in the Storage, Handling, Purification, and Sampling of Amphiphilic Mycolactone journal April 2019
Mycobacteria-derived biomarkers for tuberculosis diagnosis journal January 2017
Developing and Deploying Universal Diagnostic Platforms for One-Health Biosurveillance journal May 2018
Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications journal February 2016
Diagnosis of Tuberculosis in HIV Co-infected Individuals: Current Status, Challenges and Opportunities for the Future journal July 2017

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