Vandenbroucke-Grauls, C.M.J.E. [Promotor]Appelmelk, B.J. [Copromotor

Driessen, N.N.

DSpace at VU

Interaction between mycobacterial ManLAM and the host 
immune response
Mycobacterium tuberculosis is a 'successful' pathogen as it is 
estimated that around one-third of the world population is 
infected. Only 5 to 10% of the infected population develops 
active tuberculosis (TB), but the bacteria remain present in the 
body of infected persons in the other cases. M. tuberculosis is able 
to survive inside human cells leading to a latent, asymptomatic 
form of TB-infection, that can still become 'reactivated' TB at a 
later stage in life. Hence, the Mycobacterium-host interactions are 
both interesting, and, considering the need for new drugs and 
more effective vaccines against TB, important to study. The 
complex and thick mycobacterial cell wall contains large amounts 
of glycans, proteins, and lipids with known or hypothesized roles 
in the targeting or modulating of the host immune response, of 
which mannose-capped lipoarabinomannan (mannose-capped 
LAM; ManLAM) is one example.
    Simultaneously with the discovery of C-type lectin Dendritic 
Cell-Specic ICAM3-Grabbing Non-Integrin (DC-SIGN) as the 
major receptor on dendritic cells (DCs) for M. tuberculosis, the 
mannose cap of ManLAM appeared essential for the recognition 
of LAM by DC-SIGN. Other studies also showed that DCs can 
form a reservoir for mycobacteria and as antigen-presenting cells, 
DCs are important in the regulation of the immune response. 
Hence, the characteristics of the interaction between on the one 
hand Mycobacterium and ManLAM, and on the other hand DCs 
and DC-SIGN are of interest in the understanding of the immune 
response against M. tuberculosis: is ManLAM the key ligand in the 
interaction between mycobacteria and DC-SIGN? Does inhibition 
of this interaction prevent or reduce TB-infection? And is the 
mannose cap on LAM a virulence factor restricted to the 
slow-growing pathogenic Mycobacterium species? This thesis 
attempts to answer these questions.
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riessen
SUGAR CAPS OF MYCOBACTERIA: 
VIRULENCE FACTORS 
OR DECORATIVE ELEMENTS?
Nicole N. Driessen


Sugar caps of mycobacteria: virulence factors or decorative elements?

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Sugar caps of mycobacteria:: virulence factors or decorative elements?

VU Research Portal

VU Research PortalSugar caps of mycobacteriaDriessen, N.N.2011document versionPublisher's PDF, also known as Version of recordLink to publication in VU Research Portalcitation for published version (APA)Driessen, N. N. (2011). Sugar caps of mycobacteria: virulence factors or decorative elements?.General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            • Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            • You may not further distribute the material or use it for any profit-making activity or commercial gain            • You may freely distribute the URL identifying the publication in the public portal ?Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.E-mail address:vuresearchportal.ub@vu.nlDownload date: 21. May. 2021Interaction between mycobacterial ManLAM and the host immune responseMycobacterium tuberculosis is a 'successful' pathogen as it is estimated that around one-third of the world population is infected. Only 5 to 10% of the infected population develops active tuberculosis (TB), but the bacteria remain present in the body of infected persons in the other cases. M. tuberculosis is able to survive inside human cells leading to a latent, asymptomatic form of TB-infection, that can still become 'reactivated' TB at a later stage in life. Hence, the Mycobacterium-host interactions are both interesting, and, considering the need for new drugs and more effective vaccines against TB, important to study. The complex and thick mycobacterial cell wall contains large amounts of glycans, proteins, and lipids with known or hypothesized roles in the targeting or modulating of the host immune response, of which mannose-capped lipoarabinomannan (mannose-capped LAM; ManLAM) is one example.    Simultaneously with the discovery of C-type lectin Dendritic Cell-Specic ICAM3-Grabbing Non-Integrin (DC-SIGN) as the major receptor on dendritic cells (DCs) for M. tuberculosis, the mannose cap of ManLAM appeared essential for the recognition of LAM by DC-SIGN. Other studies also showed that DCs can form a reservoir for mycobacteria and as antigen-presenting cells, DCs are important in the regulation of the immune response. Hence, the characteristics of the interaction between on the one hand Mycobacterium and ManLAM, and on the other hand DCs and DC-SIGN are of interest in the understanding of the immune response against M. tuberculosis: is ManLAM the key ligand in the interaction between mycobacteria and DC-SIGN? Does inhibition of this interaction prevent or reduce TB-infection? And is the mannose cap on LAM a virulence factor restricted to the slow-growing pathogenic Mycobacterium species? This thesis attempts to answer these questions.SUGAR CAPS OF MYCOBACTERIA:  VIRULENCE FACTORS OR DECORATIVE ELEMENTS?Nicole N. DriessenSUGAR CAPS OF MYCOBACTERIA: VIRULENCE FACTORS OR DECORATIVE ELEMENTS?Nicole N. Driessen

Sugar caps of mycobacteria: virulence factors or decorative elements?

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