Ingestion, Immunity, and Infection: Nutrition and Viral Respiratory Tract Infections

Abstract

Respiratory infections place a heavy burden on the health care system, particularly in the winter months. Individuals with a vulnerable immune system, such as very young children and the elderly, and those with an immune deficiency, are at increased risk of contracting a respiratory infection. Most respiratory infections are relatively mild and affect the upper respiratory tract only, but other infections can be more serious. These can lead to pneumonia and be life-threatening in vulnerable groups. Rather than focus entirely on treating the symptoms of infectious disease, optimizing immune responsiveness to the pathogens causing these infections may help steer towards a more favorable outcome. Nutrition may have a role in such prevention through different immune supporting mechanisms. Nutrition contributes to the normal functioning of the immune system, with various nutrients acting as energy sources and building blocks during the immune response. Many micronutrients (vitamins and minerals) act as regulators of molecular responses of immune cells to infection. It is well described that chronic undernutrition as well as specific micronutrient deficiencies impair many aspects of the immune response and make individuals more susceptible to infectious diseases, especially in the respiratory and gastrointestinal tracts. In addition, other dietary components such as proteins, pre-, pro- and synbiotics, and also animal- and plant-derived bioactive components can further support the immune system. Both the innate and adaptive defense systems contribute to active antiviral respiratory tract immunity. The initial response to viral airway infections is through recognition by the innate immune system of viral components leading to activation of adaptive immune cells in the form of cytotoxic T cells, the production of neutralizing antibodies and the induction of memory T and B cell responses. The aim of this review is to describe the effects of a range different dietary components on anti-infective innate as well as adaptive immune responses and to propose mechanisms by which they may interact with the immune system in the respiratory tract.

Keywords: elderly; immunity; infant; infection; nutrition; respiratory virus.

Figure 1

Throughout the life course (infant, child to adult, elderly) the immune system changes in composition and activity. Innate immunity is already present at birth and quickly matures (purple line). For adaptive immune defense infants rely on placental transfer and mothers’ milk for their first period (pink section). During development, the adaptive immune system phenotype changes from Th2 dominant [i.e. tolerant (green)] to Th1 dominant [i.e. inflammatory (red)]. At later age, specific functions of innate and adaptive immunity become less efficient (purple and red arrows). Th, T helper.

Figure 2

Exposure routes and potential concerted immunomodulatory effects of food components. The route of administration determines the sites of immunomodulation. As a result of nasal exposure (the route that respiratory pathogens follow) pathogens or intranasal vaccines lead to IgA production in upper and lower airways and the vaginal area, and oral exposure leads to IgA production in the upper airways, breast and digestive system. Clinical studies have demonstrated support of respiratory immunity by many food components, whereas preclinical, ex vivo and in vitro studies identified possible mechanisms. For instance, milk-derived HMOs, pre- and probiotics modify the microbiome and SCFA production; vitamins A, C and D improve epithelial barrier integrity; vitamin D induces anti-microbial protein (AMP) secretion and acetate anti-viral interferon secretion in epithelial cells; viral adhesion and infection is reduced by zinc, bIgG, lactoferrin or HMOs; iron supports immune cell development and migration; bIgG and NDPs induce innate immune training and as a results increased cytokine and chemokine production; zinc and vitamin C support Th1 activity and IFN-γ and IL-2 release; and selenium and vitamin C support antibody production. AMP, anti-microbial peptide; HMO, human milk oligosaccharides; IFN-γ, interferon gamma; IL-2, interleukin-2; SCFA, short chain fatty acid. This figure was created with BioRender.com.

Figure 3

Foods are ingested and enter the gastrointestinal tract via the mouth and respiratory pathogens via the nasal cavity, both ending up in the tonsils of Waldeyer’s ring (1). Especially in infants, reflux can cause a direct interaction of the foods with the nasopharyngeal microbiota and influences their composition (2). Mixing of the food with saliva and mucus (based on charge and polarity) enhances the residence time in the nasopharynx (3), and as a result the still undigested food and respiratory pathogens can interact with each other and the immune tissues in the tonsil, where stasis occurs in the crypts which further lengthening the duration of interaction (4). Local immune responses can occur, during which can be modulated by the food components (5). Immune cell recirculate and home to different tissues – especially to the upper respiratory tract because of instruction by stromal cells in the tonsils – which is determined by the expression of homing receptors. This can also be influenced by food components, selectively homing, for example by vitamins, resulting in increased memory responses in the local tissues of the upper respiratory tract (6). This figure was created with BioRender.com.