Thursday, February 19, 2026 2/19/2026

Microbial Disruption of Dendritic Cell Maturation and Function

Award Number: R01AI142628
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: 09/24/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2025

Group Awards By:

View Award Description

Microbial Disruption of Dendritic Cell Maturation and Function - Several human pathogens express structurally divergent forms of lipid A, the biologically active moiety of LPS, as a strategy to evade innate immune detection and establish chronic infection. The oral mucosal pathogen Porphyromonas gingivalis intrinsically expresses underacylated lipid A moieties and can modify the phosphorylation of lipid A, leading to altered TLR4 signaling. In addition to local immunopathology, significant clinical and experimental evidence implicate P. gingivalis as risk factor for the development of chronic systemic inflammatory diseases including rheumatoid arthritis, cancer, and cardiovascular disease. Dysregulated T cell responses are believed to play a role in these inflammatory disorders. While the role of lipid A modifications in evasion of innate immune signaling is established, how this influences adaptive immune responses that contribute to dysregulation of host immunity has not been explored. Myeloid dendritic cells (DCs) and their blood monocyte precursors play an important role in bridging the innate and adaptive arms of the immune system during Gram-negative bacterial infection. TLR4 activation in these cells induces a distinct maturation phenotype that promotes their mobilization to immune T cell areas for initiation of antigen-specific immunity. Despite the wealth of studies on P. gingivalis pathogenesis in the oral cavity, the immunological mechanisms underlying P. gingivalis mediated systemic inflammation are not well defined. We propose in this application to define the impact of P. gingivalis lipid A moieties on DC responses and T cell activation that contribute to P. gingivalis mediated systemic immunopathology. We hypothesize that the different lipid A species expressed by P. gingivalis drive DC responses leading to distinct T cell activation pathways that contribute to P. gingivalis-mediated systemic inflammatory outcomes. The following Aims are proposed to test this hypothesis: Aim 1. To define the role of P. gingivalis lipid A species and TLR4 signaling in DC responses and T cell activation in vitro. Aim 2.To define the role of P. gingivalis lipid A species on TLR4- dependent DC and T cell responses following P. gingivalis oral infection. Aim 3. To define the role of P. gingivalis distinct lipid A species and DC-specific TLR4 signaling in the development of P. gingivalis induced immunopathology in vivo. Strikingly, several Gram-negative bacteria that express immune-evasive lipid A are associated with increased risk of autoimmune disease, atherosclerosis, and cancer. Thus, these studies have broad implications and will provide important insights into the mechanisms by which Gram-negative pathogens alter systemic adaptive immune responses resulting immunopathology. !


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 = $0 )
2026	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	1/26/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	8/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $586,138 )
2022	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	8/19/2022	NON-COMPETING CONTINUATION	$586,138
														Subtotal = $586,138

Issue Date FY: 2021 ( Subtotal = $612,657 )
2021	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	8/12/2021	NON-COMPETING CONTINUATION	$612,657
														Subtotal = $612,657

Issue Date FY: 2020 ( Subtotal = $620,801 )
2020	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	3	8/13/2020	NON-COMPETING CONTINUATION	$620,801
2020	2019	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	3/13/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $620,801

Issue Date FY: 2019 ( Subtotal = $622,687 )
2019	2019	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	8/1/2019	NON-COMPETING CONTINUATION	$622,687
														Subtotal = $622,687

Issue Date FY: 2018 ( Subtotal = $607,603 )
2018	2018	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	9/21/2018	NEW	$607,603
														Subtotal = $607,603

Grand Total All Awards = $3,049,886

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Microbial Disruption of Dendritic Cell Maturation and Function

Award Number: R01AI142628

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: 09/24/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer