Project 171256

Importance of PGE2 in CCR7-dependent migration of monocytes/macrophages to lymph nodes and implication in HIV-1 dissemination.

171256

Importance of PGE2 in CCR7-dependent migration of monocytes/macrophages to lymph nodes and implication in HIV-1 dissemination.

$267,126
Project Information
Study Type: Other Mechanistic_Study
Therapeutic Area: Hiv_Aids
Research Theme: Biomedical
Disease Area: HIV-1
Data Type: Canadian
Institution & Funding
Principal Investigator(s): Dumais, Nancy
Institution: Université de Sherbrooke
CIHR Institute: Infection and Immunity
Program: Operating Grant
Peer Review Committee: Virology & Viral Pathogenesis
Competition Year: 2008
Term: 3 yrs 0 mth
Abstract Summary

After initial entry of the human immunodeficiency virus (HIV), replication of the virus first occurs at the site of infection. Then the major site of replication quickly shifts to lymphoid tissues of the body, including those in lymph nodes, spleen, liver, and bone marrow. Since macrophages are important both as reservoirs and vectors for the spread of HIV in the body, the main objective of the current proposal is to determine the cell surface molecule responsible for the migration of infected monocytes/macrophages. Our preliminary results indicate that expression and functionality of CCR7, a chemokine receptor, are up-regulated in monocytes in the presence of PGE2, a pro-inflammatory molecule. This research project is designed to gain novel insights on CCR7 at the molecular, cellular and animal levels. In the first objective, we will characterize CCR7 expression by PGE2 in macrophages. In vivo and in vitro models will be used to determine the impact of HIV-1 infection on CCR7 expression in monocytes and in macrophages. The data resulting from our investigations will serve to develop strategies to stop HIV dissemination.

Research Characteristics

This project includes the following research characteristics:

Knowledge Translation Focus
Biomarker Endpoints
Study Justification

"This research project is designed to gain novel insights on CCR7 at the molecular, cellular and animal levels."

Novelty Statement

"The data resulting from our investigations will serve to develop strategies to stop HIV dissemination."

Methodology Innovation

investigating the role of PGE2 in up-regulating CCR7 expression on monocytes/macrophages and its implication for HIV-1 dissemination

Keywords
Cell Migration Chemokines And Cytokines Hiv-1 Mucosal Transmission Prostaglandins