Epidemiologic and clinical data, as well as experimental studies, suggest a bidirectional interaction between micronutrients and infectious pathogens. While nutritional deficiencies can alter several aspects of the innate and acquired immune responses to pathogens, some infectious diseases alter the nutritional status of the host and the host's ability to absorb micronutrients. Nutritional deficiencies may also influence pathogen mutations directly, affecting virulence and clinical outcome. These interactions depend on a number of other variables, including the severity of micronutrient deficiency, the age and clinical condition of the host, and a variety of environmental factors.

To address issues pertinent to understanding the role(s) of micronutrients in the control of infectious disease, the National Institute of Allergy and Infectious Diseases organized a 2-day meeting, cosponsored by the Office of Dietary Supplements, National Institutes of Health. Representatives attended from several other NIH institutes and centers, the U.S. Agency for International Development, the U.S. Department of Agriculture, the U.S. Food and Drug Administration, the Council for Responsible Nutrition, and the World Bank. The objectives of this meeting were to provide a forum for the exchange of ideas between basic scientists, nutritionists, infectious disease specialists, and clinical epidemiologists; to examine the mechanisms involved in the pathogenesis and clinical manifestations of infectious diseases, including the immunology, molecular biology, and potential direct interactions between micronutrients and pathogens; evaluate current strategies for intervention; and summarize research needs and new directions.

The workshop provided information on the effects of micronutrients on innate and adaptive immunity, mucosal immunity, cytokine production, gene expression, and intracellular signaling pathways. In addition, a session focused on the implications of basic research findings for the treatment of disease. The workshop opened with an overview on how dietary characteristics modulate immune responses. Although the field is in its infancy, areas in particular need of research include the role of micronutrients in innate and mucosal immunity, as well as the early phases of development of immune cells. Instances of direct interaction between micronutrients and pathogens were also described, for example, how a benign strain of an infectious agent can become virulent when passaged through micronutrient-deficient mice. Examples of host-pathogen interactions, in which nutrition is an important modulator, provide new opportunities for study, especially as the host's genetic background and the role of specific genes are elucidated. One potential mechanism of immune suppression is the alteration of cytokine responses. Molecular studies using gene knock-out mice also provided new information about nutrient transport proteins and their relationship to normal immunity.

At the conclusion of the workshop, a panel of experts, including basic scientists, infectious disease specialists, and clinical epidemiologists, submitted recommendations for future research: the development of a panel of assays that could be used for general screening of a nutrient's impact on immunocompetence; the need to define reproducible molecular and immunologic biomarkers that can be used in human and animal studies; the need to continue basic mechanistic studies on both the role of micronutrients as antioxidants or as regulatory molecules within the immune system and the effects of micronutrient status on the decline of immune function in the elderly; the need to encourage more efficient use of transgenic knock-outs and other appropriate animal models, as well as the use of microarray technology, by investigators in this area of research; the need for investigators to link basic molecular, mechanistic studies with field work in areas of endemic infectious diseases of greatest public health importance; the need for innovative approaches for combining nutritional supplementation and immunotherapy in new forms of intervention; and the need to recruit young investigators with state-of-the-art immunology skills and promote collaborative research with nutrition or infectious disease professionals.

As a result of this workshop, an open LISTSERV has been created for continued interaction among interested parties in the field. The Journal of Infectious Diseases plans to publish the proceedings of the workshop in a supplement in early 2000. For additional information, contact Christopher E. Taylor, telephone: 301-496-5305; e-mail: ct18m@nih.gov; or Elizabeth Higgs, telephone: 301-496-2544; e-mail: eh63a@nih.gov

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