Molecular Basis of Human Phagocyte Interactions With Bacterial Pathogens



Status:Recruiting
Healthy:No
Age Range:21 - 65
Updated:2/17/2019
Start Date:February 12, 2001
Contact:Frank R DeLeo, Ph.D.
Email:fdeleo@niaid.nih.gov
Phone:(406) 363-9448

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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....

Human phagocytic cells such as polymorphonuclear leukocytes (neutrophils or 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 bacterial
pathogens have devised means to evade normal phagocyte responses and cause severe disease 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.

- 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.
We found this trial at
1
site
903 South 4th Street
Hamilton, Montana 59840
?
mi
from
Hamilton, MT
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