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Investigation of the role of type 2 innate lymphoid cells in the pathogenesis of dengue infection

Award Number: R21AI125886
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: 06/15/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2019

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Investigation of the role of type 2 innate lymphoid cells in the pathogenesis of dengue infection - Dengue viral infections are one of the most rapidly emerging mosquito borne viral infections in the world, resulting in a huge economic burden in affected countries. Currently there is no licensed vaccine to prevent dengue, nor an effective specific drug for its treatment. Severe forms of dengue infection is characterized by vascular leak leading to shock and haemorrhage, which is thought to occur as a result of complex interactions between the virus, host genetics and the immune system. Innate like lymphoid cells (ILCs) are a recently identified population of haematopoietic effector lymphoid cells, which are predominantly tissue resident. The ILC subtype that predominantly produces type 2 cytokines (IL-4, IL-5 and IL-13) are known as ILC type 2 (ILC2s) and have shown to be important in the pathogenesis of atopic eczema and allergic asthma. Elevated type 2 cytokines are present in the blood of individuals with acute severe dengue suggesting that ILC2 could be a source. Although the source of these cytokines was previously thought to be from Th2 cells, we found that dengue- specific T cells are not the primary source of these cytokines in acute infection. Preliminary investigations done by Graham Ogg’s lab in ILC2s in acute dengue infection, showed that ILC2s are greatly expanded in patients with acute dengue infection, when compared to healthy seronegative individuals, in whom ILC2s are rarely detected in peripheral blood. In addition, the frequency of ILC2s negatively correlated with platelet counts, which is a marker of disease severity. It has been shown that monocytes and dendritic cells, are significantly more permissive to infection with the dengue virus in the presence of IL-4 and IL-13. In acute dengue infection, monocytes and dendritic cells have shown to be the main cell types infected with the virus. In addition, studies on determining risk factors for hospitalization due to dengue infection in a large cohort of individuals (n=1689) in Sri Lanka done by Gathsaurie Malavige’s group, showed that both bronchial asthma and allergic rhinitis were significantly associated with a higher risk. Collectively, these data suggest that since ILC2s are greatly expanded during acute dengue infection and since monocytes and dendritic cells are more permissive to infection in the presence of type 2 cytokines, ILC2s could be playing a role in the pathogenesis of acute dengue. By understanding the role of ILC2 in disease pathogenesis, we aim to identify new targets for therapeutic intervention.


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: 2019 ( Subtotal = -$12,069 )
2019	2017	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE	OX1 2JD		GBR	Allergy and Infectious Diseases Research	000	2	9/20/2019	NON-COMPETING CONTINUATION	-$12,069
														Subtotal = -$12,069

Issue Date FY: 2017 ( Subtotal = $137,500 )
2017	2017	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE	OX1 2JD		GBR	Allergy and Infectious Diseases Research	000	2	5/17/2017	NON-COMPETING CONTINUATION	$137,500
														Subtotal = $137,500

Issue Date FY: 2016 ( Subtotal = $137,500 )
2016	2016	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	000	1	6/15/2016	NEW	$137,500
														Subtotal = $137,500

Grand Total All Awards = $262,931

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Investigation of the role of type 2 innate lymphoid cells in the pathogenesis of dengue infection

Award Number: R21AI125886

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: 06/15/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2019

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