Suppression of immunoglobulin production in human peripheral blood mononuclear cells by monocytes via secretion of heavy-chain ferritin

Yamashita, Makiko; Harada, Gakuro; Matsumoto, Sanae; Aiba, Yoshihiro; Ichikawa, Akira; Fujiki, Toshiyuki; Udono, Miyako; Kabayama, Shigeru; Yoshida, Tadashi; Zhang, Pingbo; Fujii, Hiroshi; Shirahata, Sanetaka; Katakura, Yoshinori

doi:10.1016/j.imbio.2013.08.011

Cited by 11 publications

(7 citation statements)

References 24 publications

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“…In humans, T and B lymphocytes bind FTH directly, though the precise receptor remains unknown (36,67). In vitro, this binding has immunosuppressive effects impairing T-cell proliferation and B-cell maturation and immunoglobulin production (67)(68)(69). Recent work suggests that the inhibitory functions of FTH are largely IL-10 mediated.…”

Section: Ferritin and Lymphocyte Modulationmentioning

confidence: 99%

Hyperferritinemia and inflammation

Kernan

Carcillo

2017

International Immunology

477

407

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Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high levels indicative of primary or secondary hemochromatosis. However, further work has shown that iron, redox biology and inflammation are inexorably linked. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation. Additionally, hyperferritinemia is a key acute-phase reactants, used by clinicians as an indication for therapeutic intervention, aimed at controlling inflammation in high-risk patients. One school of thought maintains that hyperferritinemia is an 'innocent bystander' biomarker of uncontrolled inflammation that can be used to gauge effectiveness of intervention. Other schools of thought maintain that ferritin induction could be a protective negative regulatory loop. Others maintain that ferritin is a key mediator of immune dysregulation, especially in extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects. There is a clear need for further investigation of the role of ferritin in uncontrolled inflammatory conditions both as a biomarker and mediator of disease because its occurrence identifies patients with high mortality risk and its resolution predicts their improved survival.

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Section: Ferritin and Lymphocyte Modulationmentioning

confidence: 99%

Hyperferritinemia and inflammation

Kernan

Carcillo

2017

International Immunology

477

407

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“…Our previous study identified FTH1 expression in 3-day-old ducklings infected with DHV-1 from a cDNA library using a suppression subtractive hybridization (SSH) technique . Meanwhile, several reports suggested that FHP1 plays a role in inhibiting oxidative stress and apoptosis (Berberat et al 2003;Storr et al 2009;Yamashita et al 2014). In this study, we established an experimental model of DHV-1 infection of ducklings and analyzed the expression of duFTH1 mRNA in the liver and kidney.…”

Section: Discussionmentioning

confidence: 97%

Ferritin heavy polypeptide 1 mediates apoptosis-related gene expression of duck (Anas platyrhynchos domesticus)

Chen

Tong

et al. 2016

Can. J. Anim. Sci.

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Duck hepatitis virus type 1 (DHV-1) infection of ducklings causes hepatitis and is associated with high morbidity and mortality. Virus infection may induce apoptosis and inhibit proliferation. In humans, ferritin heavy polypeptide 1 (FTH1) has been reported to affect the development of hepatitis and inhibit apoptosis. However, the effect of duck FTH1 (duFTH1) on apoptosis in DHV-1 infected ducklings has not been investigated. Therefore, we measured duFHT1 expression in tissues of DHV-1 infected ducklings and characterized the functional effects of ectopic overexpression and endogenous downregulation of FTH1 in duck embryo fibroblasts (DEF) to elucidate possible mechanisms involved. In the present study, the expression of duFTH1 was decreased in liver and spleen after DHV-1 infection. The effects of altered FTH1 expression on expression of pro- and anti-apoptotic genes were evaluated by qPCR arrays. Decreased expressions of Caspase-3 and Caspase-8 were observed in FTH1-overexpressing DEF cells, while decreased expression of Bcl-2 was detected in FTH1 knocked down DEF cells. Our findings suggest that the regulation of FTH1 expression indirectly mediated the expression of apoptosis-related genes; the protective effect of FTH1 was associated with the inhibition of apoptosis in DEF.

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“…The analysis suggests an Ig positive regulatory effect of recombinant iron-related proteins. Unlike in mammals, suppression of Ig production in peripheral blood mononuclear cells associated with iron regulation in monocytes has been reported [63].…”

Section: Discussionmentioning

confidence: 99%

Chimeric Protein IPath® with Chelating Activity Improves Atlantic Salmon’s Immunity against Infectious Diseases

et al. 2021

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Infection processes displayed by pathogens require the acquisition of essential inorganic nutrients and trace elements from the host to survive and proliferate. Without a doubt, iron is a crucial trace metal for all living organisms and also a pivotal component in the host–parasite interactions. In particular, the host reduces the iron available to face the infectious disease, increasing iron transport proteins’ expression and activating the heme synthesis and degradation pathways. Moreover, recent findings have suggested that iron metabolism modulation in fish promotes the immune response by reducing cellular iron toxicity. We hypothesized that recombinant proteins related to iron metabolism could modulate the fish’s immune system through iron metabolism and iron-responsive genes. Here a chimeric iron transport protein (IPath®) was bioinformatically designed and then expressed in a recombinant bacterial system. The IPath® protein showed a significant chelating activity under in vitro conditions and biological activity. Taking this evidence, a vaccine candidate based on IPath® was evaluated in Atlantic salmon challenged with three different fish pathogens. Experimental trials were conducted using two fish groups: one immunized with IPath® and another injected with adjutant as the control group. After 400 accumulated thermal units (ATUs), two different infection trials were performed. In the first one, fish were infected with the bacterium Aeromonas salmonicida, and in a second trial, fish were exposed to the ectoparasite Caligus rogercresseyi and subsequently infected with the intracellular bacterium Piscirickettsia salmonis. Fish immunized with IPath® showed a significant delay in the mortality curve in response to A. salmonicida and P. salmonis infections. However, no significant differences between infected and control fish groups were observed at the end of the experiment. Notably, sea lice burden reduction was observed in vaccinated Atlantic salmon. Transcriptional analysis evidenced a high modulation of iron-homeostasis-related genes in fish vaccinated with IPath® compared to the control group during the infection. Moreover, increasing expression of Atlantic salmon IgT was associated with IPath® immunization. This study provides evidence that the IPath® protein could be used as an antigen or booster in commercial fish vaccines, improving the immune response against relevant pathogens for salmon aquaculture.

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Suppression of immunoglobulin production in human peripheral blood mononuclear cells by monocytes via secretion of heavy-chain ferritin

Cited by 11 publications

References 24 publications

Hyperferritinemia and inflammation

Hyperferritinemia and inflammation

Ferritin heavy polypeptide 1 mediates apoptosis-related gene expression of duck (Anas platyrhynchos domesticus)

Chimeric Protein IPath® with Chelating Activity Improves Atlantic Salmon’s Immunity against Infectious Diseases

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