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Plasmacytoid Dendritic Cells in HIV pathogenesis

Award Number: R01AI026806
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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DESCRIPTION (provided by applicant): Plasmacytoid dendritic cells (pDC) are the most potent type I interferon (IFN)- producing cells in the body and are considered to be the "professional IFN producing cells". pDC become both numerically and functionally deficient in HIV-infected individuals, and this dysfunction is strongly correlated with progression to opportunistic infections. In addition to evidence for important protective roles of the pDC in HIV infection, an overzealous pDC IFN-a response has also been associated with immune activation and HIV pathogenesis. The experiments in this application are based on our observations that peripheral blood pDC in viremic HIV-infected-individuals are not only numerically depleted, but are also functionally altered. Our studies since the last competing submission of this grant indicate that this numerical and functional dysfunction is contributed to by several factors including apoptosis of some circulating pDC, activation and potentially recruitment out of the periphery, as well as replacement of peripheral pDC with newly emigrated cells from the bone marrow. In addition, we have discovered that pDC preferentially take-up pieces of membrane and cytoplasm from live, virus-infected cells vs. uninfected cells and subsequently produce IFN-a and mature in response to this "nibbling". Upon interaction with HIV-infected cells, however, this process is subverted, and pDC fuse with the HIV-infected cells. We propose three specific aims to follow-up on these observations: In the first specific aim, we will investigate the requirements for, and consequences of, pDC fusion with HIV-infected cells. We will determine how different viral strains affect IFN-a production and pDC:HIV-infected cell interactions, both as cell-free viruses and as virus-infected cells. Included in these viruses will be early transmitted viruses as well as chronic-stage viruses to be obtained from CHAVI. Imaging and traditional flow cytometry will be central to our experimental approaches. In the second aim, we will determine whether pDC:T cell fusion occurs in vivo and in lymphoid tissues using three distinct approaches: first we will determine whether there is evidence of pDC:T cell fusion in peripheral blood of HIV-infected patients; second, we will determine whether pDC:HIV-infected T cell fusion occurs in tonsil suspension cells and tonsil organ culture; third, in collaboration with Dr. Christel Uittenbogaart of UCLA, we will determine whether pDC:T cell fusion occurs in HIV-infected HIS mice. In the final specific aim, we will investigate the functional significance of the different phenotypic subpopulations of pDC in individuals with and without HIV infection and will investigate pDC in the bone marrow of HIV-infected individuals. Together, the studies proposed in this application are anticipated to provide valuable new information on the biology of human pDC and the mechanisms underlying their dysfunction in HIV-1 infection.


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 = $0 )
2017	2014	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	000	20	12/2/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $410,880 )
2014	2014	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	002	20	6/16/2014	NON-COMPETING CONTINUATION	$393,525
2014	2013	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	19	3/13/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$89,880
2014	2013	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	003	19	8/5/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$17,357
2014	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	18	3/13/2014	NON-COMPETING CONTINUATION	$89,878
														Subtotal = $410,880

Issue Date FY: 2013 ( Subtotal = $396,670 )
2013	2013	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Allergy and Infectious Diseases Research	004	19	3/13/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$89,880
2013	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	002	18	8/16/2013	NON-COMPETING CONTINUATION	-$414,025
2013	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	18	5/17/2013	NON-COMPETING CONTINUATION	$414,027
2013	2013	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Allergy and Infectious Diseases Research	001	19	8/16/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$396,670
2013	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	003	18	3/13/2014	NON-COMPETING CONTINUATION	$89,878
														Subtotal = $396,670

Issue Date FY: 2012 ( Subtotal = $516,415 )
2012	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	002	17	9/13/2012	NON-COMPETING CONTINUATION	-$1,111
2012	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	17	6/7/2012	NON-COMPETING CONTINUATION	$75,960
2012	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	17	5/15/2012	NON-COMPETING CONTINUATION	$441,566
														Subtotal = $516,415

Issue Date FY: 2011 ( Subtotal = $455,161 )
2011	2011	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	16	6/3/2011	NON-COMPETING CONTINUATION	$399,358
2011	2011	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	16	7/25/2011	SUPPLEMENT FOR EXPANSION	$55,803
														Subtotal = $455,161

Issue Date FY: 2010 ( Subtotal = $403,393 )
2010	2010	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	15	5/15/2010	COMPETING CONTINUATION	$403,393
2010	2009	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Allergy and Infectious Diseases Research	000	14	5/12/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $403,393

Issue Date FY: 2009 ( Subtotal = $769,447 )
2009	2009	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07107	ESSEX	USA	Allergy and Infectious Diseases Research	000	14	11/13/2008	NON-COMPETING CONTINUATION	$325,441
2009	2009	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07107	ESSEX	USA	Trans-NIH Recovery Act Research Support	003	14	9/15/2009	SUPPLEMENT FOR EXPANSION	$377,770
2009	2009	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07107	ESSEX	USA	Trans-NIH Recovery Act Research Support	002	14	6/3/2009	SUPPLEMENT FOR EXPANSION	$30,076
2009	2009	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07107	ESSEX	USA	Allergy and Infectious Diseases Research	001	14	6/5/2009	NON-COMPETING CONTINUATION	$36,160
														Subtotal = $769,447

Issue Date FY: 2008 ( Subtotal = $361,601 )
2008	2008	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Allergy and Infectious Diseases Research	000	13	11/30/2007	NON-COMPETING CONTINUATION	$361,601
														Subtotal = $361,601

Issue Date FY: 2007 ( Subtotal = $368,605 )
2007	2007	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Allergy and Infectious Diseases Research	000	12	11/30/2006	NON-COMPETING CONTINUATION	$368,605
														Subtotal = $368,605

Issue Date FY: 2006 ( Subtotal = $379,614 )
2006	2006	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Allergy and Infectious Diseases Research	000	11	11/28/2005	NON-COMPETING CONTINUATION	$379,614
														Subtotal = $379,614

Issue Date FY: 2005 ( Subtotal = $388,750 )
2005	2005	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Microbiology and Infectious Diseases Research	000	10	11/29/2004	COMPETING CONTINUATION	$388,750
														Subtotal = $388,750

Issue Date FY: 2003 ( Subtotal = $243,620 )
2003	2003	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	30 BERGEN ST, ADM BLDG #11	NEWARK	NJ	07107	ESSEX	USA	Allergy and Infectious Diseases Research	001	9	8/27/2003	SUPPLEMENT FOR EXPANSION	$243,620
														Subtotal = $243,620

Issue Date FY: 2002 ( Subtotal = $438,301 )
2002	2002	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	30 BERGEN ST, ADM BLDG #11	NEWARK	NJ	07107	ESSEX	USA	Microbiology and Infectious Diseases Research	000	9	6/4/2002	NON-COMPETING CONTINUATION	$438,301
														Subtotal = $438,301

Issue Date FY: 2001 ( Subtotal = $449,814 )
2001	2001	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	30 BERGEN ST, ADM BLDG #11	NEWARK	NJ	07107	ESSEX	USA	Microbiology and Infectious Diseases Research	000	8	4/30/2001	NON-COMPETING CONTINUATION	$449,814
														Subtotal = $449,814

Issue Date FY: 2000 ( Subtotal = $417,039 )
2000	2000	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Microbiology and Infectious Diseases Research	001	7	8/28/2000	SUPPLEMENT FOR EXPANSION	$101,722
2000	2000	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Microbiology and Infectious Diseases Research	000	7	5/1/2000	NON-COMPETING CONTINUATION	$315,317
														Subtotal = $417,039

Issue Date FY: 1999 ( Subtotal = $300,345 )
1999	1999	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Microbiology and Infectious Diseases Research	001	6	9/29/1999	SUPPLEMENT FOR EXPANSION	$26,685
1999	1999	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Microbiology and Infectious Diseases Research	000	6	5/21/1999	COMPETING CONTINUATION	$273,660
														Subtotal = $300,345

Issue Date FY: 1998 ( Subtotal = $242,210 )
1998	1998	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Allergy and Infectious Diseases Research	000	5	11/7/1997	NON-COMPETING CONTINUATION	$242,210
														Subtotal = $242,210

Grand Total All Awards = $6,541,865

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Plasmacytoid Dendritic Cells in HIV pathogenesis

Award Number: R01AI026806

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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