Role of Vitamin A in the Immune System

Huang, Zhiyi; Liu, Yu; Qi, Guangying; Brand, David; Zheng, Song Guo

doi:10.3390/jcm7090258

Cited by 436 publications

(369 citation statements)

References 140 publications

Supporting

Mentioning

349

Contrasting

Unclassified

Order By: Relevance

“…Vitamin A deficiency results in increased susceptibility to infection by Salmonella and other enteric pathogens [13, 14]. Vitamin A deficiency causes immune dysregulation in the gut, including improper lymphoid recruitment, maturation and functional potential [15, 16]. These sweeping changes obscure the finer details of how vitamin A regulates infection outcome.…”

Section: Resultsmentioning

confidence: 99%

Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18

Iyer

Grizotte-Lake

Gordon

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractIntestinal epithelial cells (IECs) are at the forefront of host-pathogen interactions, coordinating a cascade of immune responses to confer protection against pathogens. Here we show that IEC-intrinsic vitamin A signaling restricts pathogen invasion early in the infection and subsequently activates immune cells to promote pathogen clearance. Mice blocked for retinoic acid receptor (RAR) signaling selectively in IECs (stopΔIEC) showed significantly higher Salmonella burden in colonic tissues early in the infection associated with higher luminal and systemic loads of the pathogen at later stages. Higher susceptibility of stopΔIEC mice correlated with attenuated mucosal interferon gamma (IFNγ) production by underlying immune cells. We found that, at homeostasis, the intestinal epithelium of stopΔIEC mice produced significantly lower amounts of interleukin 18 (IL-18), a potent inducer of IFNγ. Regulation of IL-18 by vitamin A was also observed in a dietary model of vitamin A supplementation. IL-18 reconstitution in stopΔIEC mice restored resistance to Salmonella by promoting epithelial cell shedding to eliminate infected cells and limit pathogen invasion early in infection. Further, IL-18 augmented IFNγ production by underlying immune cells to restrict pathogen burden and systemic spread. Our work uncovers a critical role for vitamin A in coordinating a biphasic immune response to Salmonella infection by regulating IL-18 production by IECs.Author SummaryEpithelial cells line the intestinal lumen, forming a barrier between the body and dietary and microbial contents in the lumen. Apart from absorbing nutrients from diet, these epithelial cells help mediate a stable, symbiotic relationship between microbes in the gut and the immune cells. During infection, they help co-ordinate the immune response to counter the infection. How dietary micronutrients, such as vitamin A, inform epithelial cell function during infection is poorly understood. Using a model where epithelial cells in the gut cannot respond to vitamin A signals, we find that epithelial vitamin A signaling promotes resistance to Salmonella infection. We show that, vitamin A increases the production of a key cytokine, interleukin 18, by epithelial cells. IL-18 promotes shedding of infected epithelial cells to reduce the pathogen invasion while also inducing the production of interferon gamma by immune cells to mediate pathogen clearance. Thus, epithelial cells dynamically respond to dietary vitamin A to regulate interleukin 18 production and potentiate resistance to infection.

show abstract

Section: Resultsmentioning

confidence: 99%

Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18

Iyer

Grizotte-Lake

Gordon

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Other vegetables, like carrots, spinach, and sweet potato, are rich in Vitamin A. This vitamin comprises a group of fat-soluble compounds (including retinol, retinoic acid, and β-carotene) that play an essential role in the immune function and are known to lower the susceptibility to infections [14]. For instance, isotretinoin (a derivative of vitamin A) mediates the down-regulation of angiotensin-converting enzyme 2 (ACE2), which is a crucial host cellular protein required for the entry of SARS-COV-2 in the body [15].…”

Section: The Role Of Bioactive Ingredients In Supporting the Human Immentioning

confidence: 99%

The Food Systems in the Era of the Coronavirus (COVID-19) Pandemic Crisis

Galanakis

2020

Foods

776

636

View full text Add to dashboard Cite

The World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19, broadly referred to as "coronavirus") a global pandemic, while thousands of infections and deaths are reported daily. The current article explores the food systems in the era of the COVID-19 pandemic crisis. It provides insights about the properties of bioactive ingredients of foods and herbs for the support of the human immune system against infections before discussing the possibility of COVID-19 transmission through the food chain. It also highlights the global food security issues arising from the fact that one-third of the world's population is on lockdown. Finally, it underlines the importance of sustainability in the food chain in order to avoid or reduce the frequency of relevant food and health crises in the future.

show abstract

“…including improper lymphoid recruitment, maturation and functional potential [15,16]. These sweeping changes obscure the finer details of how vitamin A regulates infection outcome.…”

Section: Introductionmentioning

confidence: 99%

Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18

et al. 2020

View full text Add to dashboard Cite

Intestinal epithelial cells (IECs) are at the forefront of host-pathogen interactions, coordinating a cascade of immune responses to protect against pathogens. Here we show that IECintrinsic vitamin A signaling restricts pathogen invasion early in the infection and subsequently activates immune cells to promote pathogen clearance. Mice blocked for retinoic acid receptor (RAR) signaling selectively in IECs (stop ΔIEC ) showed higher Salmonella burden in colonic tissues early in the infection that associated with higher luminal and systemic loads of the pathogen at later stages. Higher pathogen burden in stop ΔIEC mice correlated with attenuated mucosal interferon gamma (IFNγ) production by underlying immune cells. We found that, at homeostasis, the intestinal epithelium of stop ΔIEC mice produced significantly lower amounts of interleukin 18 (IL-18), a potent inducer of IFNγ. Regulation of IL-18 by vitamin A was also observed in a dietary model of vitamin A supplementation. IL-18 reconstitution in stop ΔIEC mice restored resistance to Salmonella by promoting epithelial cell shedding to eliminate infected cells and limit pathogen invasion early in infection. Further, IL-18 augmented IFNγ production by underlying immune cells to restrict pathogen burden and systemic spread. Our work uncovers a critical role for vitamin A in coordinating a biphasic immune response to Salmonella infection by regulating IL-18 production by IECs. Author summaryEpithelial cells line the intestinal lumen, forming a barrier between the body and dietary and microbial contents in the lumen. Apart from absorbing nutrients from diet, these epithelial cells help mediate a stable, symbiotic relationship between commensal bacteria and the immune cells. During infection, they help co-ordinate the immune response to counter the infection. How dietary micronutrients, such as vitamin A, inform epithelial cell function during infection is poorly understood. Using a model where epithelial cells in the gut cannot respond to vitamin A signals, we find that epithelial vitamin A signaling PLOS PATHOGENS PLOS Pathogens | https://doi.

show abstract

Role of Vitamin A in the Immune System

Cited by 436 publications

References 140 publications

Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18

Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18

The Food Systems in the Era of the Coronavirus (COVID-19) Pandemic Crisis

Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18

Contact Info

Product

Resources

About