Pseudomonas aeruginosa is an opportunistic human pathogen capable of causing both acute infections, such as ventilator-associated pneumonia, as well as chronic colonization and infection of the respiratory tract. Acute infections with P. aeruginosa usually progress rapidly, both in human patients and in corresponding mammalian infection models;thus, it is not surprising that innate immune responses play a significant role in controlling this pathogen. Many P. aeruginosa molecules trigger host innate immune responses. In turn, multiple host pathways are capable of responding during infection by this pathogen. This complexity can be reduced by studying the responses of specific cell populations to P. aeruginosa in vitro;the challenge then lies in understanding whether and how these responses contribute to pathogenesis in an intact host. In this application we focus on bacterial molecules that influence how P. aeruginosa is recognized by the innate immune system, on the signaling pathways that are triggered by these molecules, and on the modification of these signals by bacterial effectors. By carrying out these experiments we will significantly increase our understanding of how host-pathogen interactions shape the immune response to P. aeruginosa in the lung. Such information is a first step to developing successful immunomodulatory strategies for the treatment of acute or chronic P. aeruginosa infections.

Public Health Relevance

The ability to respond rapidly to infecting bacteria protects most individuals from developing pneumonia due to Pseudomonas aeruginosa. In this application we investigate the immune pathways that are responsible for recognizing bacteria to generate this protective response. We then ask how bacterial toxins can interrupt this rapid immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI081825-03
Application #
8306013
Study Section
Host Interactions with Bacterial Pathogens Study Section (HIBP)
Program Officer
Taylor, Christopher E,
Project Start
2010-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$425,971
Indirect Cost
$168,587
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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