Source: UNIV OF TEXAS - MEDICAL BRANCH submitted to
CHARACTERIZATION AND FUNCTIONALITY OF BOVINE LUNG DENDRITIC CELLS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
EXTENDED
Funding Source
NRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
0203948
Grant No.
2005-35204-15996
Project No.
TEXR-2005-02014
Proposal No.
2005-02014
Multistate No.
(N/A)
Program Code
44.0
Project Start Date
Jul 15, 2005
Project End Date
Aug 31, 2007
Grant Year
2005
Project Director
Shell, E. J.
Recipient Organization
UNIV OF TEXAS - MEDICAL BRANCH
(N/A)
GALVESTON,TX 77550
Performing Department
(N/A)
Non Technical Summary
A. Despite advances in dendritic cell biology, the population of lung dendritic cells and their functional capacity to interact with T cells are not well defined in any species. B. Interactions between dendritic cells and pathogens are likely to be critical in eliciting protective immune responses and in dictating the outcome of infection. A. The overall goal of this proposal is to define the subsets of dendritic cells, which are potent immune cells, in the bovine lung and examine their role in controlling and promoting recovery from a representative bacterial and viral infection. B. This information will provide a foundation for the understanding of pulmonary immunity in cattle.
Animal Health Component
100%
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113310109050%
3113410109050%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3310 - Beef cattle, live animal; 3410 - Dairy cattle, live animal;

Field Of Science
1090 - Immunology;
Goals / Objectives
The objective of this proposal is to characterize the resident dendritic cell populations in the bovine respiratory tract following infection with Mycobacterium bovis and foot-and-mouth disease virus and examine their effector functions following infection with these representative bacterial and viral pathogens.
Project Methods
Dendritic cells isolated from the bovine respiratory tract will be characterized by flow cytometry and confocal microscopy, and the location of these populations within the lung will be shown by immunohistochemistry and confocal microscopy. Reverse transcriptase PCR will be employed to examine effector functions, e.g., cytokine production, toll-like receptor expression, of dendritic cells. Additionally, the ability of these cells to drive robust cell-mediated immune responses will be examined by mixed lymphocyte reaction.

Progress 07/15/05 to 07/14/06

Outputs
Thus far, I have made several trips to the National Animal Disease Centers at Ames, IA and Plum Island, NY. During these trips, I have gotten valuable data on the characterization of pulmonary dendritic cells following infection with Mycobacterium bovis and Foot-and-mouth disease virus. During the first year, I have worked out almost all protocols necessary in order to complete the objectives of this fellowship, including characterization of specific dendritic cell markers, confocal analysis of these populations in lung and mediastinal lymph node tissue. Now that most protocols have been worked out, this year will be dedicated to completing the objectives of this fellowship by accurately characterizing pulmonary and mediastinal lymph node dendritic cells following infection with Mycobacterium bovis and Foot-and-mouth disease virus and characterizing their effector functions. This work should lead to a couple of publications.

Impacts
The pulmonary immune system is composed of a collection of distinct lymphoid tissue compartments and specialized immune cells that line the respiratory tract. The role each of these components contributes to lung immunity is poorly understood. The lung, an anatomically complex organ, has a substantial DC population that increases in number in response to various stimuli. Several areas need to be considered in order to elucidate the processes involved in lung immunity: Exactly what are the mechanisms involved in mounting immune responses in the lung without disrupting gas exchange processes and how are DCs involved in this process? Specifically, how do lung DCs drive T cell activation and not elicit responses that are deleterious to the host? Which pathogens or stimuli induce distinct DC effector functions and homing of these cells to the site of inflammation? Collectively, these questions and the overall uniqueness of lung DCs are not known in any disease model. Understanding how DCs initiate immune responses in the lung will assist the development of early intervention points and augment the development of strategies to elicit rapid responses to infection, which are necessary to protect against infection in animal populations.

Publications

  • No publications reported this period