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Modulation of macrophage biology and...

Bhatnagar, Sanchita.

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Modulation of macrophage biology and host immune response by mycobacterial lipids.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Modulation of macrophage biology and host immune response by mycobacterial lipids./
Author:	Bhatnagar, Sanchita.
Description:	189 p.
Notes:	Adviser: Jeffrey S. Schorey.
Contained By:	Dissertation Abstracts International67-11B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3243285
ISBN:	9780542984921

Modulation of macrophage biology and host immune response by mycobacterial lipids.
Bhatnagar, Sanchita.

Modulation of macrophage biology and host immune response by mycobacterial lipids. - 189 p.

Adviser: Jeffrey S. Schorey.

Thesis (Ph.D.)--University of Notre Dame, 2007.

Members of the Mycobacterium genus present a serious health threat which account for significant morbidity and mortality in humans and other species. Many pathogenic mycobacterial species maintain an intracellular life style within macrophages serving as the primary host cell. The mycobacterium's ability to modulate the macrophage function requires the expression of specific mycobacterial surface components. Moreover, a number of studies have shown that various mycobacterial surface components can promote macrophage activation. This dissertation aims to define the role of glycopeptidolipids (GPL), which are highly antigenic glycolipids, in the immune-modulation of the host and thus establish its function as an important virulence factor.

ISBN: 9780542984921Subjects--Topical Terms:

1017686
Biology, Cell.

Modulation of macrophage biology and host immune response by mycobacterial lipids.
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020 $a 9780542984921
035 $a (UMI)AAI3243285
035 $a AAI3243285
040 $a UMI $c UMI
100 1 $a Bhatnagar, Sanchita. $3 1287159
245 1 0 $a Modulation of macrophage biology and host immune response by mycobacterial lipids.
300 $a 189 p.
500 $a Adviser: Jeffrey S. Schorey.
500 $a Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6193.
502 $a Thesis (Ph.D.)--University of Notre Dame, 2007.
520 $a Members of the Mycobacterium genus present a serious health threat which account for significant morbidity and mortality in humans and other species. Many pathogenic mycobacterial species maintain an intracellular life style within macrophages serving as the primary host cell. The mycobacterium's ability to modulate the macrophage function requires the expression of specific mycobacterial surface components. Moreover, a number of studies have shown that various mycobacterial surface components can promote macrophage activation. This dissertation aims to define the role of glycopeptidolipids (GPL), which are highly antigenic glycolipids, in the immune-modulation of the host and thus establish its function as an important virulence factor.
520 $a To address the role of GPL as a virulence factor, we utilized M. avium strains either naturally lacking GPL expression or genetically altered to express modified GPL. Our studies showed that the loss of GPL or altering its structure leads to an M. avium strain which induces increased macrophage activation compared to GPL sufficient M. avium strains. Additional analysis showed attenuated virulence of GPL-deficient/modified M. avium strains in a mouse infection model.
520 $a To further understand the mechanism of action of GPL, we investigated the trafficking of GPL in primary macrophages infected with M. avium . Our studies revealed significant release and trafficking of GPL from the mycobacteria containing phagosome to a distinct endocytic compartment called the multivesicular bodies (MVB). Additional analysis showed that mycobacterial components including GPL are trafficked outside the infected cells on "exosomes". Further, we determined that exosomes purified from the culture supernatants of macrophages infected with M. avium, M. tuberculosis H37Rv or M. bovis BCG stimulate a pro-inflammatory response in uninfected macrophages.
520 $a Our studies are first to establish GPL's importance as a virulence factor in the M. avium pathogenesis. The data demonstrate a significant shedding of glycopeptidolipids in M. avium infected macrophages and its transport to the neighboring "bystander cells". This transport of mycobacterial components occur through release of exosomes extracellularly which can also act to stimulate uninfected macrophages both in vitro and in vivo. Together, our studies put forward a novel mechanism of intercellular communication mediated by exosomes which can carry mycobacterial components to neighboring cells.
590 $a School code: 0165.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Biology, Molecular. $3 1017719
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690 $a 0379
690 $a 0410
710 2 0 $a University of Notre Dame. $3 807615
773 0 $t Dissertation Abstracts International $g 67-11B.
790 $a 0165
790 1 0 $a Schorey, Jeffrey S., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3243285