Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Myeloid and lymphoid immunity-specific mechanisms of IDO mediated immunosuppression and its reversal, during TB

Award Number: R01AI134245
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: 05/16/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2031

Group Awards By:

View Award Description

Myeloid and lymphoid immunity-specific mechanisms of IDO mediated immunosuppression and its reversal, during TB - PROJECT SUMMARY We have developed a macaque model of Mtb infection, as well as Mtb/HIV co-infection, by using natural routes of Mtb infection. Prior to the initial iteration of this R01, we found that the expression of IDO (INDO, IDO1), a powerful immunosuppressant of activated CD4+ T cells, was dramatically enhanced in the lung TB granulomata of macaques in a bacterial burden specific manner (published). We have now shown that this is the case in human lung TB granulomata as well (published). Inhibition of IDO enzymatic activity by an FDA, approved, safe compound resulted in significant reduction in clinical signs of TB and increased survival (published). These events reshaped the granuloma: i) functionally granulomas from treated (IDO blockaded) animals higher expression of T cell differentiation, apoptosis, bacterial killing and lung tissue remodeling pathways; ii) greater relocation of T cells was observed to the center of the granulomata(published).Our results therefore suggested that IDO modulates a complex immune/metabolic signaling network that promotes bacterial survival, immune dysfunction and disease. Thus, we hypothesized that the inhibition of IDO was a prime target for adjunctive HDT against the multidrug resistant TB epidemic and embarked on three major studies supported by this R01. These included experiments) to study if IDO-blockade in-vivo i) could enhance granuloma performance; ii) was relevant in the setting of anti-TB chemotherapy or iii) in the setting of SIV (HIV) co-infection. During the past performance period, we made progress in each of the aims and have published most of these data, while one experiment (Aim 1) is pending publication in review. Using high-parameter flow cytometry, imaging and scRNAseq, we pinpointed the lung source of IDO. We now know that IDO is expressed primarily on IFN-responsive, recruited, inflammatory, interstitial macrophages (IMs), and secondarily on Myeloid Derived Suppressor Cells (MDSCs) that are highly recruited to the lungs during TB, and which contribute to inflammation (published). We found that IDO inhibition strongly synergizes with deliberately weak, suboptimal anti-TB therapy (ATT) (published; Aim 2). We also showed that IDO inhibition is safe in the setting of Mtb/HIV co- infection/antiretroviral therapy (ART) (published Aim 3). Finally, we showed that IDO inhibition in macaques with (LTBI-like) improves granuloma performance (in review). Here we propose to extend our findings to pinpoint the mechanisms by which IDO expression interferes with Mtb-specific adaptive immune responses using a mouse model of human-like TB granulomas, a macaque model of TB and human TB samples. We will use cutting-edge techniques including scRNAseq, single cell imaging and high parameter immune evaluations. Our proposed studies will provide novel insights into the molecular mechanisms that mediate TB progression and identify protective immune mechanisms that will inform the development of new treatment regimens and vaccines for TB.


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: 2026 ( Subtotal = $989,998 )
2026	2026	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	8	1/30/2026	COMPETING CONTINUATION	$989,998
														Subtotal = $989,998

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	7	9/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	7	3/14/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $1,130,921 )
2023	2023	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	002	7	4/14/2023	NON-COMPETING CONTINUATION	$1,130,921
2023	2020	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	001	5	1/18/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$851,458
2023	2019	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	000	3	1/18/2023	NON-COMPETING CONTINUATION	-$851,458
														Subtotal = $1,130,921

Issue Date FY: 2022 ( Subtotal = $1,319,347 )
2022	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	002	6	4/15/2022	NON-COMPETING CONTINUATION	$1,260,778
2022	2020	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	000	4	1/25/2022	NON-COMPETING CONTINUATION	-$1,018,521
2022	2020	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	001	5	1/25/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,077,090
														Subtotal = $1,319,347

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	000	4	6/23/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $1,018,521 )
2020	2020	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	000	4	4/29/2020	NON-COMPETING CONTINUATION	$1,018,521
														Subtotal = $1,018,521

Issue Date FY: 2019 ( Subtotal = $1,149,234 )
2019	2019	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	002	3	3/26/2019	NON-COMPETING CONTINUATION	$916,047
2019	2018	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	001	2	1/31/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$866,688
2019	2018	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	004	2	5/2/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
2019	2018	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Allergy and Infectious Diseases Research	003	1	5/2/2019	NEW	-$1
2019	2018	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Allergy and Infectious Diseases Research	000	1	1/31/2019	NEW	-$633,501
														Subtotal = $1,149,234

Issue Date FY: 2018 ( Subtotal = $640,007 )
2018	2018	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Allergy and Infectious Diseases Research	000	1	5/16/2018	NEW	$640,007
														Subtotal = $640,007

Grand Total All Awards = $6,248,028

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Myeloid and lymphoid immunity-specific mechanisms of IDO mediated immunosuppression and its reversal, during TB

Award Number: R01AI134245

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: 05/16/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer