Molecular Basis of Human Phagocyte Interactions With Bacterial Pathogens

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00339287
First received: June 19, 2006
Last updated: June 13, 2014
Last verified: May 2014
  Purpose

Human phagocytic cells such as polymorphonuclear leukocytes (PMNs) are readily mobilized to sites of infection and ingest microorganisms by a process known as phagocytosis. The combined effects of reactive oxygen species (ROS) and proteolytic peptides and enzymes released into forming bacterial phagosomes kill most ingested bacteria. However, many human bacterial pathogens have devised means to subvert normal phagocyte responses and the innate immune response and cause severe disease.

The overall objective of this study is to elucidate specific features of pathogen-phagocyte interactions that underlie evasion of the innate immune response or contribute to the pathophysiology of disease or inflammatory disorders. Therefore, specific projects will:

  1. Identify and characterize specific mechanisms used by pathogenic microorganisms to evade or subvert normal phagocyte responses and therefore cause disease.
  2. Investigate phagocyte response mechanisms to specific pathogenic microorganisms.
  3. Identify specific bacterial structures and/or (gene) products that dictate differences in phagocyte responses among a range of pathogens so that generalized statements can be made about the pathophysiology of disease states.

The studies will be performed using multiple techniques including state-of-the-art equipment for genomics and proteomics strategies to identify target bacterial genes/proteins of interest or those up-regulated in phagocytes. Phagocyte-pathogen interactions will be examined using fluorescence-based real-time assays and video microscopy, confocal and electron microscopy in combination with enzymatic assays for ROS production, routine biochemistry, immunology and cell biology.

Implementing these studies will require isolation of phagocytic leukocytes from venous blood of healthy human volunteers. The study population will be all-inclusive except in certain instances where individuals possess genetic defects that impair phagocyte function (e.g., myeloperoxidase-deficiency) or have altered phagocyte function due to outside influences such as recent bacterial or viral infection.

The proposed studies will likely provide new information pertinent to understanding host cell-pathogen interactions and the pathophysiology of inflammatory conditions.


Condition
Normal Neutrophil Function

Study Type: Observational
Official Title: Molecular Basis of Human Phagocyte Interactions With Bacterial Pathogens

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Neutrophil function assays. [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: February 2001
Detailed Description:

Human phagocytic cells such as polymorphonuclear leukocytes (PMNs) are readily mobilized to sites of infection and ingest microorganisms by a process known as phagocytosis. The combined effects of reactive oxygen species (ROS) and antimicrobial peptides released into forming bacterial phagosomes kill most ingested bacteria. However, many human bacterial pathogens have devised means to evade normal phagocyte responses and cause severe diseases in humans.

The overall objective of this study is to elucidate specific features of pathogen-phagocyte interactions that underlie evasion of the innate immune response or contribute to the pathophysiology of disease or inflammatory disorders. Therefore, projects will address 3 specific aims:

  1. Identify and characterize specific mechanisms used by pathogenic microorganisms to evade or subvert normal phagocyte responses and therefore cause disease.
  2. Investigate phagocyte response mechanisms to specific pathogenic microorganisms.
  3. Identify specific bacterial structures and/or (gene) products that dictate differences in phagocyte responses among a range of pathogens so that generalized statements can be made about the pathophysiology of disease states.

The studies will be performed using multiple techniques including state-of-the-art equipment for genomics and proteomics strategies to identify target bacterial genes/proteins of interest or those up-regulated in phagocytes. Phagocyte-pathogen interactions will be examined using fluorescence-based real-time assays and video microscopy, confocal and electron microscopy in combination with enzymatic assays for ROS production, routine biochemistry, immunology and cell biology.

Implementing these studies will require isolation of phagocytic leukocytes from venous blood of healthy human volunteers. The study population will be all-inclusive except in certain instances where individuals possess genetic defects that impair phagocyte function (e.g., myeloperoxidase-deficiency) or have altered phagocyte function due to outside influences such as recent bacterial or viral infection.

The proposed studies will likely provide new information pertinent to understanding host cell-pathogen interactions and the pathophysiology of inflammatory conditions.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION & EXCLUSION CRITERIA:

Volunteers will be selected from a healthy adult population, 21-65 years of age, with no known medical problems and will generally be NIH employees working at Rocky Mountain Laboratories (RML) or within the community of Hamilton, MT.

No race or gender is excluded from the donor pool and reflects the diversity of the community and that of the employees at RML.

The specific criteria for eligibility are as follows:

  • Subjects must fit the definition of healthy adults as assessed by the medical/health screening evaluations, and willing to have blood and/or tissue samples stored for future use.
  • Children are excluded.
  • Pregnant women will be identified by verbal history and are not eligible to donate blood for this protocol.
  • The study population will be all-inclusive except in certain instances where individuals possess genetic defects that impair phagocyte function (e.g., myeloperoxidase-deficiency) or have altered phagocyte function due to outside influences such as recent bacterial or viral infection.
  • Individuals below the normal hematocrit and hemoglobin ranges will be excluded from the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00339287

Contacts
Contact: Frank R DeLeo, Ph.D. (406) 363-9448 fdeleo@niaid.nih.gov

Locations
United States, Montana
NIAID, Rocky Mountain Laboratories Recruiting
Hamilton, Montana, United States, 59840
Sponsors and Collaborators
Investigators
Principal Investigator: Frank R DeLeo, Ph.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00339287     History of Changes
Other Study ID Numbers: 999901055, 01-I-N055
Study First Received: June 19, 2006
Last Updated: June 13, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Inflammation
Innate Immunity
Macrophages
Neutrophils
Pathogenesis

ClinicalTrials.gov processed this record on September 18, 2014