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REGULATION OF EARLY CYTOKINE RECEPTORS TO TB INFECTION

Award Number: R01AI054361
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 09/15/2002
PERIOD OF PERFORMANCE END DATE: 06/30/2007

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REGULATION OF EARLY CYTOKINE RECEPTORS TO TB INFECTION - DESCRIPTION (provided by applicant): The aim of these studies is to understand how the human protective immune response to tuberculosis (TB) is regulated. Our previous work suggests that the levels of inflammatory cytokines (TNF-a and IL-12) produced early in response to infection with M. tuberculosis determine the effectiveness of the Th1 response in the mouse. Clinical isolates of M. tuberculosis that fail to induce high IL-12 cause more severe disease (that is, are more virulent). In the mouse IFN-alpha/Beta (type 1 IFN) appear to downregulate the Th1 cytokine response. We hypothesize that in humans, M. tuberculosis clinical isolates that induce low levels of IL-12 and/or high levels of type 1 IFN in monocytes and dendritic cells (DC) will be more virulent, i.e., more likely to cause disease or more likely to cause severe manifestations of disease. In addition, we hypothesize that specific polyketides of M. tuberculosis are involved in induction of the differential cytokine response. To test these hypotheses we will ask the following questions: (1) Do specific M tuberculosis clinical isolates differentially induce IL-l2 in infected human monocytes/macrophages, thereby affecting the efficiency of the Th1 protective response? (2) Is the maturation and antigen presenting function of human myeloid dendritic cells (DC) differentially regulated by M. tuberculosis clinical isolates or by M. tuberculosis lipids? (3) Does IFN-a/b down regulate the development of IL-12 dependent Th1 responses in human TB? Do specific M. tuberculosis clinical isolates differentially induce IFN-a/b production by human leukocytes? To answer these questions we will examine the human leukocyte-M tuberculosis interaction in vitro using a combination of standard immunological assays (ELISA and lymphocyte proliferation; intracellular cytokine staining, FACS analysis), cell biologic assays (DC maturation) and molecular analyses of the monocyte response to infection (2-D gel electrophoresis with mass spectrometry.


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: 2006 ( Subtotal = $420,464 )
2006	2006	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	000	5	7/3/2006	NON-COMPETING CONTINUATION	$420,464
														Subtotal = $420,464

Issue Date FY: 2005 ( Subtotal = $420,654 )
2005	2005	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Microbiology and Infectious Diseases Research	000	4	6/22/2005	NON-COMPETING CONTINUATION	$420,654
														Subtotal = $420,654

Issue Date FY: 2004 ( Subtotal = $411,014 )
2004	2004	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Microbiology and Infectious Diseases Research	000	3	5/26/2004	NON-COMPETING CONTINUATION	$411,014
														Subtotal = $411,014

Issue Date FY: 2003 ( Subtotal = $400,667 )
2003	2003	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Microbiology and Infectious Diseases Research	000	2	6/18/2003	NON-COMPETING CONTINUATION	$400,667
														Subtotal = $400,667

Issue Date FY: 2002 ( Subtotal = $296,111 )
2002	2002	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Microbiology and Infectious Diseases Research	000	1	9/12/2002	NEW	$296,111
														Subtotal = $296,111

Grand Total All Awards = $1,948,910

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REGULATION OF EARLY CYTOKINE RECEPTORS TO TB INFECTION

Award Number: R01AI054361

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 09/15/2002

PERIOD OF PERFORMANCE END DATE: 06/30/2007

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