Enemy or ally? Fasting as an essential regulator of immune responses

Disease-induced anorexia is a behavioral change employed by the host upon microbial infection that induces dietray restriction by decreasing food consumption. Recent experimental data utilizing force feeding in infected mice supports the notion that anorexic behavior is a fundamental host metabolic program that can mediate either detrimental or beneficial context-dependent effects, based on the type of pathogenic challenge model. Growing evidence support the hypothesis that dietary restriction and fasting can modulate protective and pathogenic immune functions, thus improving chronic inflammation without impacting host defense against parasitic or viral infections. The ketogenic diet (KD) is a dietary intervention efficiently used to mimic fasting which induces distinct metabolic alterations in host metabolism. Recent advances have highlighted the protective effect of KD in autoimmune, inflammatory, or viral diseases, and its potential as a single/complementary candidate therapeutic approach in the clinic. Nutrition is essential for supplying an organism with sufficient energy to maintain its bodily functions. Apart from serving as an energy supply, the immunomodulatory effects of diet are emerging as a central aspect of human health. The latest evidence suggests that dietary restriction may play an important regulatory role by influencing the activation and effector functions of immune cells. However, depending on the context, nutrient restriction may have both pathogenic and beneficial effects. Here, we discuss the diverse roles of fasting programs, including ketogenesis in infection and chronic inflammation, aiming to clarify their detrimental and/or beneficial effects. Understanding these differences may help identify conditions under which dietary interventions might serve as putative effective approaches to treat various diseases. Nutrition is essential for supplying an organism with sufficient energy to maintain its bodily functions. Apart from serving as an energy supply, the immunomodulatory effects of diet are emerging as a central aspect of human health. The latest evidence suggests that dietary restriction may play an important regulatory role by influencing the activation and effector functions of immune cells. However, depending on the context, nutrient restriction may have both pathogenic and beneficial effects. Here, we discuss the diverse roles of fasting programs, including ketogenesis in infection and chronic inflammation, aiming to clarify their detrimental and/or beneficial effects. Understanding these differences may help identify conditions under which dietary interventions might serve as putative effective approaches to treat various diseases. an energy sensor activated by increasing ratios of AMP/ATP and ADP/ATP that regulates catabolic metabolism to increase the generation of ATP. the ASC protein consists of a pyrin domain (PYD) and a caspase recruitment domain (CARD). The oligomerization of ASCPYD into filaments and the cross-linking of these filaments by ASCCARD leads to the formation of ASC specks and inflammasome activation. a procedure for collecting respiratory secretions to analyze the cellular and non-cellular components. ‘wasting’ syndrome characterized by exhaustion of nutrient stores, extreme weight loss, and the proteolysis of muscle tissue leading to an exhaustion of amino acid supplies. a dietary intervention in which the caloric intake is reduced to a certain percentage of the ad libitum intake. an experimental autoimmune condition that is commonly used to mimic aspects of multiple sclerosis, an autoimmune condition affecting the central nervous system. cellular stress induced in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum; induced when the demand for protein folding exceeds the capacity of the endoplasmic reticulum for protein folding. a condition of refraining from food intake for a defined period. a diet containing increased fatty acid content, designed to induce obesity in animal models. a distinct subset of innate lymphoid cells, responsible for maintaining tissue homeostasis at barrier sites. Chronic activation of ILC2 causes allergen-induced airway inflammation by increasing mucus production and eosinophil recruitment. a common behavioral change of the host upon infection; characterized by loss of appetite followed by decreased food consumption and weight loss. a disease characterized by chronic inflammation of the gastrointestinal tract. Its subtypes include Crohn’s disease and ulcerative colitis. an eating pattern cycling between periods of fasting and food intake (e.g., food intake is restricted to a period of 24 h, followed by fasting for 24 h). a diet that mimics a fasting state through reduced protein and carbohydrate, but increased fat contents. This diet forces the liver to produce ketone bodies from fat, which are subsequently used as the major fuel supply for distal organs such as the brain. toxicity caused by the accumulation of free fatty acids in cells. a condition referring to deficiencies, excesses, or imbalances in energy and nutrient uptake. a central metabolic sensor promoting anabolic metabolism and cell growth by suppressing catabolic processes. a multimeric intracellular protein complex. Activation and assembly of this complex activates caspase-1, the release of the cytokines IL-1β and IL-18, and triggers an inflammatory form of cell death called pyroptosis. a branch of glucose metabolism, important for nucleotide synthesis and generation of NADPH. a nuclear hormone receptor and master regulator of lipid metabolism. a synthetic analog of double-stranded RNA that activates Toll-like receptor 3. It is a widely used ligand to mimic viral infections. a byproduct of metabolic pathways; serve as both cellular signaling molecules and antimicrobial agents. An imbalance in reactive oxygen species production and antioxidant systems results in oxidative stress. a coordinated set of adaptive behavioral changes such as lethargy, social withdrawal, and loss of appetite that develop during the course of an infection. long-lived antigen-specific T cells that remain in the body after the elimination of an infection and are rapidly reactivated upon re-exposure to their specific antigen. a distinct subpopulation of CD4+ effector T cells mediating immune responses against viral and bacterial infections; characterized by the expression of the transcription factor T-bet and the production of cytokines IL-2 and interferon-γ. a distinct subpopulation of CD4+ effector T cells mediating immune responses against parasites, allergens, and toxins; characterized by the expression of the transcription factor GATA-3 and the production of cytokines IL-4, IL-5, and IL-13. a distinct subpopulation of CD4+ effector T cells playing an important role in host defense against extracellular pathogens as well as in autoimmune diseases; characterized by the expression of the transcription factor RORγt and the production of cytokines IL-17 and IL-22. a distinct subpopulation of CD4+ effector T cells required for maintaining self-tolerance and immune cell homeostasis; characterized by the expression of the transcription factor FOXP3. inflammation characterized by the production of the cytokines IL-4, IL-5, IL-9, and IL-13 by GATA-3+ cell types; involved in the defense against parasitic infections and allergic diseases. a cellular stress response activated from an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum. a type of T cell expressing one gamma and one delta T-cell receptor chain. γδ T cells are predominately located at barrier sites such as the gut, lung, and skin but also adipose tissue and uterus.