Effect of vitamin D on immune response of respiratory system against influenzas and COVID-19: A review

Vitamin D could decrease the risk of viral infections with regulation of the immune system response against viral activity. Proper level of 25(OH)D decreases the risk of chronic respiratory tract infections (RTIs), malignancies, hypertension, cardiovascular disease, and diabetes mellitus. Vitamin D can decrease risk of RTIs through some mechanisms. Adequate levels of vitamin D can decrease the level of pro-inflammatory cytokines which predominantly release from innate immune cells. It also can preserve tight junctions in the base membrane. Vitamin D may eliminate enveloped viruses by activating cathelicidin (a protein in the membrane of neutrophils, macrophages, and epithelial cells). These processes can reduce the risk of a cytokine storm and severe pneumonia. Clinical trials have shown the beneficial influences of vitamin D in decreasing the risk of viral pneumonia, dengue fever, hepatitis B, hepatitis C, and herpes infections.Keywords: Vitamin D, influenza, covid-19, innate immune cells, infections

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Macrophages and Dendritic Cells Are Not the Major Source of Pro-Inflammatory Cytokines Upon SARS-CoV-2 Infection

Frontiers in Immunology ◽

10.3389/fimmu.2021.647824 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marc A. Niles ◽

Patricia Gogesch ◽

Stefanie Kronhart ◽

Samira Ortega Iannazzo ◽

Georg Kochs ◽

...

Keyword(s):

Dendritic Cells ◽

Inflammatory Cytokines ◽

Immune Cells ◽

Influenza A ◽

Innate Immune ◽

Innate Immune Cells ◽

M2 Macrophages ◽

Myeloid Dendritic Cells ◽

M1 And M2 Macrophages ◽

Pro Inflammatory Cytokines

The exact role of innate immune cells upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their contribution to the formation of the corona virus-induced disease (COVID)-19 associated cytokine storm is not yet fully understood. We show that human in vitro differentiated myeloid dendritic cells (mDC) as well as M1 and M2 macrophages are susceptible to infection with SARS-CoV-2 but are not productively infected. Furthermore, infected mDC, M1-, and M2 macrophages show only slight changes in their activation status. Surprisingly, none of the infected innate immune cells produced the pro-inflammatory cytokines interleukin (IL)−6, tumor necrosis factor (TNF)-α, or interferon (IFN)−α. Moreover, even in co-infection experiments using different stimuli, as well as non-influenza (non-flu) or influenza A (flu) viruses, only very minor IL-6 production was induced. In summary, we conclude that mDC and macrophages are unlikely the source of the first wave of cytokines upon infection with SARS-CoV-2.

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Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22168697 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8697

Author(s):

Diana Reimers ◽

Manuela Vallejo-Muñoz ◽

María José Casarejos ◽

Adriano Jimenez-Escrig ◽

Rafael Gonzalo-Gobernado ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune Cells ◽

Immunohistochemical Study ◽

Transgenic Mouse Model ◽

Innate Immune ◽

Innate Immune Cells ◽

Danger Signals ◽

Model Of Alzheimer’S Disease ◽

Pro Inflammatory Cytokines

Neuroinflammation is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), and is notably dependent on age. One important inflammatory pathway exerted by innate immune cells of the nervous system in response to danger signals is mediated by inflammasomes (IF) and leads to the generation of potent pro-inflammatory cytokines. The protein “apoptosis-associated speck-like protein containing a caspase recruitment domain” (ASC) modulates IF activation but has also other functions which are crucial in AD. We intended to characterize immunohistochemically ASC and pattern recognition receptors (PRR) of IF in the hippocampus (HP) of the transgenic mouse model Tg2576 (APP), in which amyloid-beta (Aβ) pathology is directly dependent on age. We show in old-aged APP a significant amount of ASC in microglia and astrocytes associated withAβ plaques, in the absence of PRR described by others in glial cells. In addition, APP developed foci with clusters of extracellular ASC granules not spatiallyrelated to Aβ plaques, which density correlated with the advanced age of mice and AD development. Clusters were associated withspecific astrocytes characterized by their enlarged ring-shaped process terminals, ASC content, and frequent perivascular location. Their possible implication in ASC clearance and propagation of inflammation is discussed.

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Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Cellular and Molecular Life Sciences ◽

10.1007/s00018-020-03540-9 ◽

2020 ◽

Vol 77 (22) ◽

pp. 4485-4503 ◽

Cited By ~ 3

Author(s):

Samuel Lara-Reyna ◽

Jonathan Holbrook ◽

Heledd H. Jarosz-Griffiths ◽

Daniel Peckham ◽

Michael F. McDermott

Keyword(s):

Cystic Fibrosis ◽

Immune Cells ◽

Viral Infections ◽

Opportunistic Infections ◽

Airway Epithelial Cells ◽

Innate Immune ◽

Signalling Pathways ◽

Sweat Glands ◽

Innate Immune Cells ◽

Cftr Mutations

Abstract Cystic fibrosis (CF) is one of the most common life-limiting recessive genetic disorders in Caucasians, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF is a multi-organ disease that involves the lungs, pancreas, sweat glands, digestive and reproductive systems and several other tissues. This debilitating condition is associated with recurrent lower respiratory tract bacterial and viral infections, as well as inflammatory complications that may eventually lead to pulmonary failure. Immune cells play a crucial role in protecting the organs against opportunistic infections and also in the regulation of tissue homeostasis. Innate immune cells are generally affected by CFTR mutations in patients with CF, leading to dysregulation of several cellular signalling pathways that are in continuous use by these cells to elicit a proper immune response. There is substantial evidence to show that airway epithelial cells, neutrophils, monocytes and macrophages all contribute to the pathogenesis of CF, underlying the importance of the CFTR in innate immune responses. The goal of this review is to put into context the important role of the CFTR in different innate immune cells and how CFTR dysfunction contributes to the pathogenesis of CF, highlighting several signalling pathways that may be dysregulated in cells with CFTR mutations.

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Cytokine networking of innate immunity cells: a potential target of therapy

Clinical Science ◽

10.1042/cs20130497 ◽

2014 ◽

Vol 126 (9) ◽

pp. 593-612 ◽

Cited By ~ 123

Author(s):

Ilja Striz ◽

Eva Brabcova ◽

Libor Kolesar ◽

Alena Sekerkova

Keyword(s):

T Cells ◽

Epithelial Cells ◽

Regulatory T Cells ◽

Inflammatory Cytokines ◽

Immune Cells ◽

Innate Immune ◽

Lymphoid Cells ◽

Extracellular Matrix Protein ◽

Innate Immune Cells ◽

Pro Inflammatory Cytokines

Innate immune cells, particularly macrophages and epithelial cells, play a key role in multiple layers of immune responses. Alarmins and pro-inflammatory cytokines from the IL (interleukin)-1 and TNF (tumour necrosis factor) families initiate the cascade of events by inducing chemokine release from bystander cells and by the up-regulation of adhesion molecules required for transendothelial trafficking of immune cells. Furthermore, innate cytokines produced by dendritic cells, macrophages, epithelial cells and innate lymphoid cells seem to play a critical role in polarization of helper T-cell cytokine profiles into specific subsets of Th1/Th2/Th17 effector cells or regulatory T-cells. Lastly, the innate immune system down-regulates effector mechanisms and restores homoeostasis in injured tissue via cytokines from the IL-10 and TGF (transforming growth factor) families mainly released from macrophages, preferentially the M2 subset, which have a capacity to induce regulatory T-cells, inhibit the production of pro-inflammatory cytokines and induce healing of the tissue by regulating extracellular matrix protein deposition and angiogenesis. Cytokines produced by innate immune cells represent an attractive target for therapeutic intervention, and multiple molecules are currently being tested clinically in patients with inflammatory bowel disease, rheumatoid arthritis, systemic diseases, autoinflammatory syndromes, fibrosing processes or malignancies. In addition to the already widely used blockers of TNFα and the tested inhibitors of IL-1 and IL-6, multiple therapeutic molecules are currently in clinical trials targeting TNF-related molecules [APRIL (a proliferation-inducing ligand) and BAFF (B-cell-activating factor belonging to the TNF family)], chemokine receptors, IL-17, TGFβ and other cytokines.

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Immunoporosis: Role of Innate Immune Cells in Osteoporosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.687037 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yogesh Saxena ◽

Sanjeev Routh ◽

Arunika Mukhopadhaya

Keyword(s):

Inflammatory Cytokines ◽

Immune Cells ◽

Inflammatory Mediators ◽

Innate Immune ◽

Innate Immune Cells ◽

Myeloid Lineage ◽

Molecular Patterns ◽

The Impact ◽

Pro Inflammatory Cytokines

Osteoporosis or porous bone disorder is the result of an imbalance in an otherwise highly balanced physiological process known as ‘bone remodeling’. The immune system is intricately involved in bone physiology as well as pathologies. Inflammatory diseases are often correlated with osteoporosis. Inflammatory mediators such as reactive oxygen species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the bone cells and play a role in the pathogenesis of osteoporosis. Recently, Srivastava et al. (Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of Osteoporosis-Role of T Cells. Frontiers in immunology. 2018;9:657) have coined the term “immunoporosis” to emphasize the role of immune cells in the pathology of osteoporosis. Accumulated pieces of evidence suggest both innate and adaptive immune cells contribute to osteoporosis. However, innate cells are the major effectors of inflammation. They sense various triggers to inflammation such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), cellular stress, etc., thus producing pro-inflammatory mediators that play a critical role in the pathogenesis of osteoporosis. In this review, we have discussed the role of the innate immune cells in great detail and divided these cells into different sections in a systemic manner. In the beginning, we talked about cells of the myeloid lineage, including macrophages, monocytes, and dendritic cells. This group of cells explicitly influences the skeletal system by the action of production of pro-inflammatory cytokines and can transdifferentiate into osteoclast. Other cells of the myeloid lineage, such as neutrophils, eosinophils, and mast cells, largely impact osteoporosis via the production of pro-inflammatory cytokines. Further, we talked about the cells of the lymphoid lineage, including natural killer cells and innate lymphoid cells, which share innate-like properties and play a role in osteoporosis. In addition to various innate immune cells, we also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. We also highlighted the studies regarding the impact of physiological and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing, ultimately triggering osteoporosis.

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A Proinflammatory Effect of the β-Glucan from Pleurotus cornucopiae Mushroom on Macrophage Action

Mediators of Inflammation ◽

10.1155/2017/8402405 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Ken-ichiro Minato ◽

Akihiro Ohara ◽

Masashi Mizuno

Keyword(s):

Vitamin D ◽

Immune Response ◽

Immune Cells ◽

Treated Group ◽

Peritoneal Macrophages ◽

Innate Immune ◽

Control Group ◽

Innate Immune Cells ◽

Proinflammatory Effect ◽

And Control

PCPS from P. citrinopileatus mushroom extract is a β-1,6-glucan possessing a proinflammatory effect on innate immune cells. The PCPS stimulated THP-1 macrophages to secrete significant levels of TNF. Moreover, the mRNA expressions of TNF and IL-1β were significantly enhanced by PCPS treatment. However, the PCPS did not induce to express both IL-12 and IL-10 mRNA in the macrophages. Next, the P. cornucopiae extract (containing mainly PCPS) treatment against mice showed significant increases in TNF and IL-1β mRNA expressions in the peritoneal macrophages of them. In this study, the expression levels of IFNγ mRNA in the spleen were almost the same between the extract- (PCPS-) treated group and control group. However, the expression of IL-4 mRNA showed a lower level in the extract-treated group than that in the control. Our results suggested that the PCPS could induce proinflammatory action in the immune response. In addition, the proinflammatory effect of the PCPS on THP-1 was enhanced by 5′-GMP-Na, while it was reduced by vitamin D2. These two compounds are majorly contained in the P. citrinopileatus mushroom. Therefore, these results suggested that the P. citrinopileatus mushroom might contain other immune regulative compounds, such as vitamin D2, as well as PCPS.

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In Vivo Activation of the Intracrine Vitamin D Pathway in Innate Immune Cells and Mammary Tissue during a Bacterial Infection

PLoS ONE ◽

10.1371/journal.pone.0015469 ◽

2010 ◽

Vol 5 (11) ◽

pp. e15469 ◽

Cited By ~ 37

Author(s):

Corwin D. Nelson ◽

Timothy A. Reinhardt ◽

Donald C. Beitz ◽

John D. Lippolis

Keyword(s):

Vitamin D ◽

Bacterial Infection ◽

Immune Cells ◽

Innate Immune ◽

Mammary Tissue ◽

Innate Immune Cells

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Toll-Like Receptors in Natural Killer Cells and Their Application for Immunotherapy

Journal of Immunology Research ◽

10.1155/2020/2045860 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Ji-Yoon Noh ◽

Suk Ran Yoon ◽

Tae-Don Kim ◽

Inpyo Choi ◽

Haiyoung Jung

Keyword(s):

Immune Responses ◽

Nk Cells ◽

Immune Cells ◽

Viral Infections ◽

Nk Cell ◽

Innate Immune ◽

Innate Immune Cells ◽

Innate Immune Responses ◽

Toll Like Receptors ◽

Microbial Infection

Innate immunity represents the first barrier for host defense against microbial infection. Toll-like receptors (TLRs) are the most well-defined PRRs with respect to PAMP recognition and induction of innate immune responses. They recognize pathogen-associated molecular patterns (PAMPs) and trigger innate immune responses by inducing inflammatory cytokines, chemokines, antigen-presenting molecules, and costimulatory molecules. TLRs are expressed either on the cell surface or within endosomes of innate immune cells. NK cells are one of the innate immune cells and also express TLRs to recognize or respond to PAMPs. TLRs in NK cells induce the innate immune responses against bacterial and viral infections via inducing NK cytotoxicity and cytokine production. In this review, we will discuss the expression and cellular function of TLRs in NK cells and also introduce some therapeutic applications of TLR agonists for NK cell-mediated immunotherapy.

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