Entangling of Nutrition, Metabolism, and Immunity : Infectious Microbes & Diseases

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Entangling of Nutrition, Metabolism, and Immunity

Wang, Fudi1,2

Editor(s): van der Veen, Stijn

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Infectious Microbes & Diseases 3(4):p 173-174, December 2021. | DOI: 10.1097/IM9.0000000000000075
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Nutrition is well recognized as an important contributor to immunity and to the risk and severity of various infections. During the COVID-19 pandemic, a balanced healthy diet to support our immune system for fighting the viral infections has become more apparent than ever. The immune response is tightly coupled with an increased rate of metabolism, which requires energy sources derived from the diet. Therefore, diverse and sufficient nutrients and their metabolism are essential to maintain the proper immune functions. With this Themed Collection on Nutrition, Metabolism, and Immunity in Infectious Microbes & Diseases, we provide an overview of the interconnected link of nutrition, metabolism, and immunity, and also highlight some of the most exciting scientific advances of the field.

In the perspective of the impact of imbalanced nutrition on infectious diseases, Yang and colleagues highlighted that both undernutrition and overnutrition negatively affect immune responses, which leads to increased susceptibility to infectious diseases.1 Conversely, an infectious condition reshapes the nutritional status through decreasing essential nutrients, including carbohydrates, lipids, proteins, as well as vitamins and minerals. Under such conditions, insufficient nutrients may consequently influence various important biological processes, such as energy supply and hormone homeostasis. On the theme of the gut microbiome, Yang and colleagues highlighted the involvement of intestinal microbes in host amino acid metabolism and resistance to intestinal infections, and the advantages of germ-free animal models for studying the underlying mechanisms.2 Along similar lines, a recent study reported that vitamin D deficiency was found in 22% of COVID-19 patients.3 Interestingly, emerging studies support the notion that vaccine efficacy could be compromised in populations with iron deficiency and anemia.

As both the host and pathogens require trace minerals, such as iron and zinc, for maintaining health and survival, a primary line of host defense is to sequester and starve invading pathogens of trace minerals during infection. Na-Phatthalung and colleagues overviewed our current understanding of the critical role of zinc homeostasis in macrophage-mediated defensive mechanisms upon bacterial infections.4 High levels of intracellular zinc lead to increased antimicrobial capacities, such as nitric oxide and reactive oxygen species production, phagocytosis, and antigen presentation, in macrophages by suppressing the nuclear factor-kappa B (NF-κB) signaling pathway, whereas zinc deficiency promotes hyper-inflammation, oxidative stress, and cell death. Gao and colleagues summarized the most recent findings with respect to nutrition-related pathways of autophagy, metal homeostasis, and the nutrition-driven morphological switches in two major human fungal pathogens, Cryptococcus neoformans and Candida albicans, which are the leading causes of protean clinical manifestations and candidiasis in immunocompromised patients, especially people with human immunodeficiency virus/acquired immunodeficiency syndrome.5

On the front line of host responses, Ye and colleagues overviewed metabolic regulation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, the cytosolic multiprotein complex assembled by different mechanisms.6 Glycolysis, lipid, and amino acid metabolisms activate the NLRP3 inflammasome followed by activation of caspase-1 and subsequent maturation of interleukin (IL)-1β and IL-18, which provide protection against infectious pathogens. In addition to innate immune responses, Bai and colleagues highlighted the effect of forkhead box P3 (FOXP3+) regulatory T cells (Tregs) on infectious and inflammatory diseases.7 FOXP3+ Tregs possess important functions in protecting the host from excessive immune responses by secreting immunosuppressive cytokines, such as IL-10, IL-35, and transforming growth factor-β (TGF-β). Activation of Tregs alleviates tissue damage and controls inflammation at the early stage of infection.

At the interface between host and pathogens, Zhao and colleagues demonstrated that efficient activation of Notch targets by zymosan, a product of yeast cell wall, needs cooperation between dectin-1 and toll like receptor 2 (TLR2) signaling in dendritic cells.8 Remarkably, expression of Hes1, a Notch target gene, was induced through up-regulation of cFos, a transcription factor acting downstream of TLR2- and dectin-1/Syk-induced signaling cascades of mitogen-activated protein kinases (MAPKs). This discovery explains how Syk and TLR2-mediated mitogen-activated protein kinase signaling is activated in response to pathogens that stimulate pattern recognition receptors promoting microbial clearance. In addition, Li and colleagues reviewed mTOR-mediated cell death and infection.9 The mammalian target of rapamycin (mTOR) pathway and the current clinical use of rapamycin were highlighted. In addition, the role of the mTOR pathway in immune cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis, was summarized. The potential clinical application of mTOR inhibitor in COVID-19 was also discussed. Meng and colleagues highlighted recent progress of metabolic control of γδ T cells.10 The influence of metabolic pathways and nutrients on γδ T cell function was summarized. It is believed that metabolic features of γδ T cell subsets provide novel insights into interventions targeting γδ T cells in disease control.

Mounting evidence supports the essentiality of intertwined nutrition, metabolism, and immunity in maintaining human health. While much progress has been made, more exciting biology remains to be explored on the nutritional and metabolic immune horizon. Recently, the potential modulatory effects of the gut microbiota have drawn more attention on interactions between nutrition and the immune system in health and disease. We hope that this Themed Collection provides a platform to bring researchers, clinicians, and readers together to develop potential novel nutritional, metabolic, and immunological therapeutics into promising future avenues of precision medicine.


The author thanks Prof. Junxia Min and Dr. Pinanong Na-Phatthalung at Zhejiang University School of Medicine for valuable discussion suggestions.


[1]. Yang F, Yang Y, Zeng L, Chen Y, Zeng G. Nutrition metabolism and infections. Infect Microb Dis 2021;3(3):134–141.
[2]. Yang Y, Bin P, Tao S, et al. Evaluation of the mechanisms underlying amino acid and microbiota interactions in intestinal infections using germ-free animals. Infect Microb Dis 2021;3(2):79–86.
[3]. Radujkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M, Merle U. Vitamin D deficiency and outcome of COVID-19 patients. Nutrients 2020;12(9):2757.
[4]. Na-Phatthalung P, Min J, Wang F. Macrophage-mediated defensive mechanisms involving zinc homeostasis in bacterial infection. Infect Microb Dis 2021;3(4):175–182.
[5]. Gao X, Fu Y, Ding C. Nutrition-associated processes govern fungal pathogenicity. Infect Microb Dis 2021;3(2):69–78.
[6]. Ye Q, Chen S, Wang D. Metabolic regulation of the NLRP3 inflammasome. Infect Microb Dis 2021;3(4):183–186.
[7]. Bai Y, Gao F, Li D, et al. The effect of FOXP3+ regulatory T cells on infectious and inflammatory diseases. Infect Microb Dis 2021;3(4):187–197.
[8]. Zhao Y, Ju C, Au K, et al. Engagement of TLR and dectin-1/Syk signaling Is required for activation of Notch targets in dendritic cells. Infect Microb Dis 2021;3(2):101–108.
[9]. Li S, Wang Q, Su B. mTOR-mediated cell death and infection. Infect Microb Dis 2021;3(2):57–68.
[10]. Meng Z, Cao G, Yang Q, Yang H, Hao J, Yin Z. Metabolic control of γδ T cell function. Infect Microb Dis 2021;3(3):142–148.

nutrition; metabolism; immunity

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.