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Role of Commensal Microbiota in Stressor-Induced Immunomodulation

Award Number: R21AI107238
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2015
PERIOD OF PERFORMANCE END DATE: 01/31/2017

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Role of Commensal Microbiota in Stressor-Induced Immunomodulation - DESCRIPTION (provided by applicant): Chronic inflammatory diseases affect millions of Americans each year, and have a significant medical, psychosocial, and economic impact on both the patient and on society. Multiple sclerosis is a chronic, degenerative neurological disorder involving immune-mediated inflammatory demyelinating processes, and is significantly exacerbated by comorbid conditions, such as stress and anxiety. Despite this knowledge, the mechanisms by which this occurs are not yet well understood. The studies in this proposal will test the highly novel and integrative hypothesis that the intestinal microbiota are involved in stressor-induced enhancement of systemic inflammation that leads to symptom exacerbation in an animal model of multiple sclerosis. We have made the exciting discovery that the intestinal microbiota are necessary for stressor-induced increases in splenic IL-1¿ to occur. This is important, because IL-1 plays a central role in the development of many chronic inflammatory diseases, including multiple sclerosis. How the microbiota lead to increased IL-1 during stressor exposure, as well as the effects on chronic inflammatory diseases, is not well understood. During repeated social defeat, commensal microbes can translocate from their primary niche to the interior of the body. Because there is accumulating evidence that neuroendocrine hormones, such as sympathetic nervous system-derived catecholamine hormones, can impact microbial populations, Aim 1 will test whether stressor-induced activation of the sympathetic nervous system leads to translocation of commensal microbiota. As further confirmation that microbial translocation is necessary for stressor-induced immunoenhancement to occur, Aim 2 will test the hypothesis that stressor-induced increases in splenic IL-1¿ are dependent upon both macrophage pattern recognition receptor signaling and inflammasome formation. Finally, to determine whether the microbiota contribute to stressor-induced exacerbation of a chronic disease, a widely used animal model of multiple sclerosis, namely experimental autoimmune encephalomyelitis (EAE) will be employed. The effects of repeated social defeat on EAE progression will be determined in germfree mice (i.e., mice that have never come into contact with commensal microbes) and conventional mice. By integrating the results of Aims 1, 2, and 3, we will identify novel mechanisms by which stressor exposure can exacerbate a chronic inflammatory disease. These findings would ultimately facilitate the rational design and use of microbiota-targeting therapeutics to treat chronic disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2017 ( Subtotal = -$1,277 )
2017	2015	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	3	4/28/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,277
														Subtotal = -$1,277

Issue Date FY: 2015 ( Subtotal = $194,140 )
2015	2015	Research Institute at Nationwide`s Children`s Hospital	700 CHILDREN`S DRIVE	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	004	3	9/2/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$405
2015	2015	Research Institute at Nationwide`s Children`s Hospital	700 CHILDREN`S DRIVE	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	3	8/14/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$105,856
2015	2015	OHIO STATE UNIVERSITY	1800 CANNON DR/700 LINCOLN TOW	COLUMBUS	OH	43210	FRANKLIN	USA	Allergy and Infectious Diseases Research	002	2	8/15/2015	NON-COMPETING CONTINUATION	-$104,216
2015	2015	OHIO STATE UNIVERSITY	1800 CANNON DR/700 LINCOLN TOW	COLUMBUS	OH	43210	FRANKLIN	USA	Allergy and Infectious Diseases Research	003	2	9/1/2015	NON-COMPETING CONTINUATION	$405
2015	2015	OHIO STATE UNIVERSITY	1800 CANNON DR/700 LINCOLN TOW	COLUMBUS	OH	43210	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	2	1/12/2015	NON-COMPETING CONTINUATION	$192,500
														Subtotal = $194,140

Issue Date FY: 2014 ( Subtotal = $230,688 )
2014	2014	OHIO STATE UNIVERSITY	1800 CANNON DR/700 LINCOLN TOW	COLUMBUS	OH	43210	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	1	1/22/2014	NEW	$207,619
2014	2014	OHIO STATE UNIVERSITY	1800 CANNON DR/700 LINCOLN TOW	COLUMBUS	OH	43210	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	1	4/24/2014	NEW	$23,069
														Subtotal = $230,688

Grand Total All Awards = $423,551

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Role of Commensal Microbiota in Stressor-Induced Immunomodulation

Award Number: R21AI107238

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2015

PERIOD OF PERFORMANCE END DATE: 01/31/2017

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