Studies in humans as well as experimental animal models have shown that
nutritional deficiencies can alter the ability of the host immune system
to respond to a variety of parasitic and bacterial infections. Furthermore,
some infectious diseases alter the nutritional status of the hosts and
the ability to absorb micronutrients. It is important that micronutrient
studies have a clear testable hypothesis and designed to understand basic
mechanisms involved. A major problem associated with the development of
effective prevention strategies is the lack of understanding of the basic
mechanisms involved in the alteration of host responses. It is anticipated
that this mechanistic approach will bring scientific rigor to the field
of micronutrients which is clearly of major significance to the manifestation
of infectious diseases. Large micronutrient distribution programs should
benefit from studies designed to understand the mechanisms by which micronutrients
influence the expression of tropical infectious diseases. This would make
rational intervention more feasible. NIH has a clear leadership responsibility
to provide research guidance in this area.
Program Agenda
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8:30 |
Welcome and Opening Remarks - NIH Staff |
Plenary Talk |
8:40 |
"Nutritional Modulation of Resistance to Infectious Diseases"
Dr. Kirk Klasing, Univ. of California, Davis |
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Micronutrient Effects on Innate Immunity and Hematopoiesis
Moderator, Dr. Adrianne Bendich, Smith Kline Beecham, Parsippany, NJ |
9:10 |
"Micronutrients and Non-specific Immunity"
Dr. Kent Erickson, Univ. California, Davis |
9:35 |
"Modulation of Human Monocyte Function by Dietary Carotenoids"
Dr. David Hughes, Norwich Research Park, UK |
10:00 |
"Important Adaptive Changes made in Lymphopoiesis and
Myelopoiesis During Zinc Deficiency"
Dr. Pamela Fraker, Michigan State Univ., East Lansing, MI |
10:25 - 10:45 |
Break
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Micronutrient Effects on Adaptive Immunity
Moderator, Dr. Donald Bundy, World Bank, Washington, DC |
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10:45 |
"Vitamin A-Induced Modulation of Antibody Responses"
Dr. Richard Semba, Johns Hopkins Univ., Baltimore, MD |
11:10 |
"Immune Responses in a Vitamin A Deficiency State: Changes
in Cellularity and Antibody Responses"
Dr. A. Catharine Ross, Penn State University, University Park, PA |
11:35 |
"Micronutrients and Malaria: Changes in Antibody and
Cytokine Production"
Dr. Anuraj Shankar, Johns Hopkins Univ., Baltimore, MD |
12:00 - 12:30 |
General Discussion/ Critical Questions
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List of "Suggested" Critical Questions |
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Most studies of mechanisms look at one specific nutrient. Is there any
evidence of synergy (or antagonism) between different micronutrients in
terms of immunomodulation?
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What is the influence of disease on the absorption of micronutrients and
on micronutrient status?
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A reduction of plasma retinol, zinc and iron are a consequence of Infection.
Why does this happen? Low plasma iron stimulates greater activity of macrophage
nitric oxide synthase activity which is bacteriocidal. Is the reduction
in retinol a device to reduce losses of urinary retinol which are associated
with fever? Alternatively, does low retinol increase immunocompetance?
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How does Vitamin A (or other micronutrients) affect the number and differentiation
of bone marrow progenitors? Are significant effects seen with a moderate
deficiency of the particular micronutrient in question?
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What is the interaction of vitamin A and acute phase response to infection/injury?
When is this interaction "beneficial" to the host and when does it represent
maladaptation?
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12:30 - 1:30 |
Lunch
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PM SESSION DAY 1 |
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Micronutrients and Gene Expression
Moderator, Dr. Richard Deckelbaum, Columbia University, NY |
|
1:30 |
"Zinc Deficiency Alters Th2 Immune Response to Gut Nematodes"
Dr. Marilyn Scott, McGill Univ, Canada |
1:55 |
"Vitamin A and gut Immunity"
Dr. David Thurnham, Univ. of Ulster, N. Ireland |
2:20 |
"The Effect of Stress and Starvation on Bacterial Virulence
Strategies"
Dr. John Alverdy, Univ. of Chicago, Chicago, Illinois |
2:45 - 3:00 |
Break
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|
Micronutrients and Gene Expression
Moderator, Dr. Richard Deckelbaum, Columbia University, NY |
|
3:00 |
"Expression of Cysteine-Rich Intestinal Protein, a Zinc
Finger Protein, Affects Th1/Th2 Cytokine Balance"
Dr. Robert Cousins, Univ. of Fl., Gainesville, FL |
3:25 |
"Zinc and Apoptosis in Respiratory Epithelium"
Dr. Peter Zalewski, Univ. Adelaide, Woodville, Australia |
3:50 |
"Influence of Antioxidant Nutrients on Viral Infection"
Dr. Melinda Beck, Univ. N. Carolina, Chapel Hill, NC |
4:15 |
"Retinol-Binding Protein, Retinoid Transport and Immunity"
Dr. William Blaner, Columbia Univ., New York, NY) |
|
4:40 - 5:00 |
General Discussion/ Critical questions
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List of "Suggested" Critical Questions |
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How can researchers make the best use of the many emerging transgenic and
gene-deletion (knock-out) mice?
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What animal models are particularly suited for evaluating the immunomodulatory
effects of nutrients on the maturation, activation and effector functions
of the various immune cells types and tissues? Which biomarkes, in vivo
tests, provide the best insights when considering the modulatory influences
of nutrients on immunocompetence.
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What molecular studies can be done to address micronutrient modulation
of immune function during infection in humans? How do we bridge the large
gap between molecular biology and nutritional epidemiology?
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When, where and how do the pathways of retinoic acid and cytokine signaling
intersect? Do Th1 type cytokines markedly enhance Th2 responses in vitamin
A (or other micronutrient) deficiency? Are there key intermediates, such
as IRF, STAT or JAK/TYK signaling pathways?
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Why is plasma zinc moved to the liver in infection? Is it just to reduce
losses via the gut in diarrhoea or does low plasma Zn upregulate aspects
of the immune system?
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|
6:30 |
Speakers Dinner at Jean-Michel Restaurant, Old Georgetown
Road/Democracy Blvd |
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AM SESSION DAY 2 |
8:15 - 8:35 |
Summary of Day 1 |
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Micronutrient Effects on Intracellular
Signalling Pathways
Moderator, Dr. Kent Erickson, Univ. California, Davis |
|
8:35 |
"Effects of Dietary Fatty Acids on T cell Activation,
a T Cell Receptor (TcR)-Mediated Signaling in a Murine Model"
Dr. David McMurray, Texas A & M, College Station, TX |
8:50 |
"Dietary Omega-3 Fatty Acids Adversly Effects IL-12 and
IFNg Responses During Murine Listeriosis"
Dr. Kevin Fritsche, Univ. of Missouri, Columbia, MO |
9:15 |
"Giardia lamblia - the Life-Cycle of a Primitive Eukaryote
is Modulated by its Lipid Environment"
Dr. Richard Deckelbaum, Columbia Univ., NY, and Dr. Ted Nash, NIAID |
9:40 - 9:55 |
Break
|
|
Modulation of Cytokine Responses by Micronutrients
Moderator, Dr. David Hughes, Norwich Research Park, UK |
|
9:55 |
"Effects of Zinc on Th1 and Th2 Cytokine Shifts"
Dr. Ananda Prasad, Wayne State Univ., Detroit, MI |
10:20 |
"Effects on Selenium Deficiency on Cytokine Responses"
Dr. Marianna Baum, Univ. of Miami, Miami, FL |
10:45 |
"Effects of Inadequate Copper Status on Cytokine Expression
in Immune Cells"
Dr. Mark Failla, Univ. N. Carolina, Greensboro, NC |
11:10 |
"Antioxidant Cytokines and Influenza Infection in the
Aged"
Dr. Simin Meydani, Tufts Univ., Boston, MA |
|
11:35 - 11:45 |
General Discussion/Critical Questions
|
List of "Suggested" Critical Questions |
-
Since compartmentalization is an important component of the way the immune
response is regulated in vivo, how does the reliance on tissue immune cells
(e.g., peritoneal macrophages, splenocytes) in most rodent studies versus
peripheral blood immune cells for human studies effect the comparability
of these data?
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Are cell lines particularly useful in assessing the impact of nutrient
status on specific aspects (B cells, Macrophages or interactions among)
of innate vs acquired immunity?
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How should one select the most appropriate cell or animal model that would
relate these studies to humans?
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Does vitamin A deficiency represent a condition of chronic (mild) inflammation
that biases the immune system towards Th1 type of response?
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11:45 - 12:45 |
Lunch
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Implications for Treatment and Disease
Moderators, Drs. Richard Guerrant, Univ. Virginia and Frances Davidson,
USAID, Washington DC |
|
12:45 |
"The Immunological Evaluation of the Nutritionally At
Risk Host"
Dr. Carl Keen (Univ. California, Davis, CA) |
1:10 |
"Transfusional Iron Overload: An Analytical Model of
Nutrient Immune Interactions"
Dr. Susanna Cunningham Rundles, Cornell Univ., New York, NY |
1:35 |
"Nutritional Modulation of Immune Responses: Implications
for Disease"
Dr. Wafaie Fawzi, Harvard University, Cambridge, MA |
1:50 |
"Implications for International Research and Child Health"
Dr. Gerald Keusch, Forgarty International Center, Bethesda, MD |
|
2:15 - 2:45 |
General Discussion/Critical Questions
|
List of "Suggested" Critical Questions |
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What are the practical issues pertaining to the inclusion of state-of-the-art
immunological parameters in field studies?
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What are the public health implications of nutritional immunology? Can
we design specific micronutrient interventions for specific infectious
diseases? Is it time to form a professional society of nutritional immunology?
What has had more of an impact on infectious disease case fatality rates
in developing countries--better nutrition or technologically advanced medicine?
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What are the consequences of marginal vs frank deficiencies and are there
markers of marginal deficiencies applicable to field situations? Are micronutrient
effects linked to macronutrient status?
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Considering the importance of the ultimate move from "bench to bedside",
in the field of nutrition and infectious diseases, what factors/issues
should be considered in establishing guidelines/standards. For example,
is a Board of nutrition and ID experts needed?
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2:45 - 3:00 |
Break
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3:00 - 3:30 |
Discussion of Objectives
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3:30 - 3:45 |
Workshop Summary and Recommendations for Future Research
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3:45 - 4:00 |
Funding Opportunities
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