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Immunomodulatory pathways and metabo...

Bhargava, Prerna.

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Immunomodulatory pathways and metabolism.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Immunomodulatory pathways and metabolism./
Author:	Bhargava, Prerna.
Description:	140 p.
Notes:	Source: Dissertation Abstracts International, Volume: 74-06(E), Section: B.
Contained By:	Dissertation Abstracts International74-06B(E).
Subject:	Biology, General. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3553398
ISBN:	9781267928733

Immunomodulatory pathways and metabolism.
Bhargava, Prerna.

Immunomodulatory pathways and metabolism. - 140 p.

Source: Dissertation Abstracts International, Volume: 74-06(E), Section: B.

Thesis (Ph.D.)--Harvard University, 2013.

Energy metabolism plays a vital role in normal physiology, adaptive responses and host defense mechanisms. Research throughout the last decade has shown evidence that immune pathways communicate with metabolic pathways to alter the metabolic status in response to physiological or pathological signals. In this thesis, I will explore how immunomodulatory molecules affect metabolic homeostasis and conversely, how metabolic sensing pathways modulate immune responses. The first part my work utilizes an immunomodulatory sugar motif to determine mechanisms by which immune cells influence metabolism. Specifically, I show in chapter 2 that lacto-N-fucopentaose III (LNFPIII), a motif used by pathogens to attenuate inflammation, is capable of improving systemic insulin sensitivity by increasing Il-10 production in macrophages and dendritic cells and subsequently improving white adipose tissue insulin sensitivity. Chapter 3 will address the observation that this same glycan is capable of directly activating Fxralpha in hepatocytes. This direct effect manifests as a reduction in high-fat-diet-induced hepatic triglyceride accumulation and improvement in liver function. Lastly, in chapter 4, I will discuss the role of metabolic regulators in the macrophage and how this affects the ability of the macrophage to kill bacteria. Specifically, I will show that lipid sensing nuclear receptors, such as Ppardelta and Ppargamma, are critical regulators of phagosomal function and bacterial killing. Macrophage-specific deletion of these receptors prevents efficient killing of Streptococcus pneumoniae, the causative bacterium in many cases of respiratory pneumonia. Ligand activation improves survival, suggesting a potential therapeutic role for Ppar activation during infection. Taken together, all the data suggest a critical role for the evolutionary interaction between metabolic and immune pathways. These interactions may be important when developing new therapeutics for complex metabolic and immunological dysfunctions.

ISBN: 9781267928733Subjects--Topical Terms:

1018625
Biology, General.

Immunomodulatory pathways and metabolism.
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100 1 $a Bhargava, Prerna. $3 2101572
245 1 0 $a Immunomodulatory pathways and metabolism.
300 $a 140 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-06(E), Section: B.
500 $a Adviser: Chih-Hao Lee.
502 $a Thesis (Ph.D.)--Harvard University, 2013.
520 $a Energy metabolism plays a vital role in normal physiology, adaptive responses and host defense mechanisms. Research throughout the last decade has shown evidence that immune pathways communicate with metabolic pathways to alter the metabolic status in response to physiological or pathological signals. In this thesis, I will explore how immunomodulatory molecules affect metabolic homeostasis and conversely, how metabolic sensing pathways modulate immune responses. The first part my work utilizes an immunomodulatory sugar motif to determine mechanisms by which immune cells influence metabolism. Specifically, I show in chapter 2 that lacto-N-fucopentaose III (LNFPIII), a motif used by pathogens to attenuate inflammation, is capable of improving systemic insulin sensitivity by increasing Il-10 production in macrophages and dendritic cells and subsequently improving white adipose tissue insulin sensitivity. Chapter 3 will address the observation that this same glycan is capable of directly activating Fxralpha in hepatocytes. This direct effect manifests as a reduction in high-fat-diet-induced hepatic triglyceride accumulation and improvement in liver function. Lastly, in chapter 4, I will discuss the role of metabolic regulators in the macrophage and how this affects the ability of the macrophage to kill bacteria. Specifically, I will show that lipid sensing nuclear receptors, such as Ppardelta and Ppargamma, are critical regulators of phagosomal function and bacterial killing. Macrophage-specific deletion of these receptors prevents efficient killing of Streptococcus pneumoniae, the causative bacterium in many cases of respiratory pneumonia. Ligand activation improves survival, suggesting a potential therapeutic role for Ppar activation during infection. Taken together, all the data suggest a critical role for the evolutionary interaction between metabolic and immune pathways. These interactions may be important when developing new therapeutics for complex metabolic and immunological dysfunctions.
590 $a School code: 0084.
650 4 $a Biology, General. $3 1018625
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Biology, Cell. $3 1017686
690 $a 0306
690 $a 0982
690 $a 0379
710 2 $a Harvard University. $b Biological Sciences in Public Health. $3 2101573
773 0 $t Dissertation Abstracts International $g 74-06B(E).
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791 $a Ph.D.
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793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3553398