Vitamin D upregulates the macrophage complement receptor immunoglobulin in innate immunity to microbial pathogens

Small, Annabelle; Harvey, Sarah; Kaur, Jasbinder; Putty, Trishni; Quach, Alex; Munawara, Usma; Perveen, Khalida; McPhee, Andrew J; Hii, Charles S.; Fèrrante, Antonio

doi:10.1038/s42003-021-01943-3

Cited by 36 publications

(28 citation statements)

References 32 publications

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“…More recent work has shown that vitamin D can activate antimicrobial activity in both human monocytes and macrophages through the induction of cathelicidin following TLR2/1 heterodimer activation ( Liu et al., 2006 ; Liu et al., 2007 ). Phagocytic capacity has also been shown to increase in macrophages treated with 1,25(OH) 2 D 3 , perhaps through upregulation of complement receptor immunoglobulin (CRIg) ( Small et al., 2021 ). This mechanism could support the finding in our study showing a significant increase in total MAP uptake for clinical animals, as other recent reports have described CRIg functioning as a pattern recognition receptor (PRR) for gram-negative bacteria and parasites ( Zeng et al., 2016 ; Liu et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne’s Disease

Wherry

Dassanayake

Casas

et al. 2022

Front. Cell. Infect. Microbiol.

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Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of ruminant enteritis, targets intestinal macrophages. During infection, macrophages contribute to mucosal inflammation and development of granulomas in the small intestine which worsens as disease progression occurs. Vitamin D3 is an immunomodulatory steroid hormone with beneficial roles in host-pathogen interactions. Few studies have investigated immunologic roles of 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in cattle, particularly cattle infected with MAP. This study examined the effects of exogenous vitamin D3 on immune responses of monocyte derived macrophages (MDMs) isolated from dairy cattle naturally infected with MAP. MDMs were pre-treated with ± 100 ng/ml 25(OH)D3 or ± 4 ng/ml 1,25(OH)2D3, then incubated 24 hrs with live MAP in the presence of their respective pre-treatment concentrations. Following treatment with either vitamin D3 analog, phagocytosis of MAP by MDMs was significantly greater in clinically infected animals, with a greater amount of live and dead bacteria. Clinical cows had significantly less CD40 surface expression on MDMs compared to subclinical cows and noninfected controls. 1,25(OH)2D3 also significantly increased nitrite production in MAP infected cows. 1,25(OH)2D3 treatment played a key role in upregulating secretion of pro-inflammatory cytokines IL-1β and IL-12 while downregulating IL-10, IL-6, and IFN-γ. 1,25(OH)2D3 also negatively regulated transcripts of CYP24A1, CYP27B1, DEFB7, NOS2, and IL10. Results from this study demonstrate that vitamin D3 compounds, but mainly 1,25(OH)2D3, modulate both pro- and anti-inflammatory immune responses in dairy cattle infected with MAP, impacting the bacterial viability within the macrophage.

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Section: Discussionmentioning

confidence: 99%

Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne’s Disease

Wherry

Dassanayake

Casas

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Vitamin D induces the expression of antimicrobial proteins such as cathelicidin and β-defensin-2 [46,47], playing an important role in the first response to microbial infections On the other hand, vitamin D skews the polarization of monocytes to a less pro-inflammatory phenotype, altering the cytokine secretion profile by changing the MAPK1 signaling [48,49]. Additionally, vitamin D impairs the maturation of monocytes to dendritic cells [50], while favoring the phagocytic capacity of macrophages though the induction of complement receptors [51].…”

Section: Effect On Innate Immune Cellsmentioning

confidence: 99%

Effect of Vitamin D on Graft-Versus-Host Disease

Rodríguez-Gil¹,

Carrillo‐Cruz²,

Marrero-Cepeda³

et al. 2022

Preprint

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The different cell subsets of the immune system express vitamin D receptor (VDR). Through VDR, vitamin D exerts different functions which influences on immune responses, as previously shown in different preclinical models. Based on this background, retrospective studies have explored the impact of vitamin D levels on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation, showing that vitamin D deficiency is related to an increased risk of complications, especially graft-versus-host disease. These results have been confirmed in a prospective cohorts trial, although further studies are required to confirm this data. In addition, the role of vitamin D on the treatment of hematologic malignancies has also been explored. Considering this dual effect both on the immune system as well as on tumor cells in patients with hematologic malignancies, vitamin D might be useful in this setting both to decrease graft-versus-host disease and relapse rates.

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“…Together, vitamin D promotes innate immunity through the expression of cathelicidin and β-defensin, improves autophagy, accelerates and cooperates with IFN, and affects complement activation [59].…”

Section: Antiviral Activity Of Vitamin D and The Innate Immune Responsementioning

confidence: 99%

Putative Role of Vitamin D for COVID-19 Vaccination

Chiu

Zheng

et al. 2021

IJMS

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Severe acute respiratory syndrome coronavirus 2 is a new, highly pathogenic virus that has recently elicited a global pandemic called the 2019 coronavirus disease (COVID-19). COVID-19 is characterized by significant immune dysfunction, which is caused by strong but unregulated innate immunity with depressed adaptive immunity. Reduced and delayed responses to interferons (IFN-I/IFN-III) can increase the synthesis of proinflammatory cytokines and extensive immune cell infiltration into the airways, leading to pulmonary disease. The development of effective treatments for severe COVID-19 patients relies on our knowledge of the pathophysiological components of this imbalanced innate immune response. Strategies to address innate response factors will be essential. Significant efforts are currently underway to develop vaccines against SARS-CoV-2. COVID-19 vaccines, such as inactivated DNA, mRNA, and protein subunit vaccines, have already been applied in clinical use. Various vaccines display different levels of effectiveness, and it is important to continue to optimize and update their composition in order to increase their effectiveness. However, due to the continuous emergence of variant viruses, improving the immunity of the general public may also increase the effectiveness of the vaccines. Many observational studies have demonstrated that serum levels of vitamin D are inversely correlated with the incidence or severity of COVID-19. Extensive evidence has shown that vitamin D supplementation could be vital in mitigating the progression of COVID-19 to reduce its severity. Vitamin D defends against SARS-CoV-2 through a complex mechanism through interactions between the modulation of innate and adaptive immune reactions, ACE2 expression, and inhibition of the renin-angiotensin system (RAS). However, it remains unclear whether Vit-D also plays an important role in the effectiveness of different COVID-19 vaccines. Based on analysis of the molecular mechanism involved, we speculated that vit-D, via various immune signaling pathways, plays a complementary role in the development of vaccine efficacy.

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Vitamin D upregulates the macrophage complement receptor immunoglobulin in innate immunity to microbial pathogens

Cited by 36 publications

References 32 publications

Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne’s Disease

Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne’s Disease

Effect of Vitamin D on Graft-Versus-Host Disease

Putative Role of Vitamin D for COVID-19 Vaccination

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