CD32a receptor in health and disease

Low-affinity Fcγ-receptors that recognize the Fc portion of immunoglobulin (Ig) molecules, usually being in antigen-bound state, thus representing a link between innate and adaptive immunity. They play a significant role in inflammatory and infectious diseases. Among them, a separate FcγRII family (CD32) is discerned, which is characterized by transmission of intracellular signal independently of the common γ-chain, they have one α-chain containing two extracellular immunoglobulin-like domains. FcγRII receptors are present in almost all cells of the innate immune system: monocytes and macrophages, neutrophils, eosinophils, dendritic cells, as well as on B-lymphocytes and platelets. They perform two main functions: target recognition, facilitation of phagocytosis and destruction of antibody-opsonized cells by monocytes/ macrophages (including pathogenic cells). In parallel, the phagocytes are activated via the cytokine synthesis stimulation. The FcγRIIA (CD32a) and FcγRIIC (CD32c) activating receptors, like as FcγRIIB (CD32b) inhibiting receptors are present among the members of the FcγRII family. The low-affinity FcγRII receptors bind to IgG, with immune complexes being their natural ligands. High levels of immune complexes are usually found in both chronic viral infections and autoimmune diseases. There are shown polymorphic variants of the CD32a gene, which can affect the receptor function, and, thereby, causing susceptibility for different infections, influence the development of autoimmune diseases and primary immunodeficiencies. Activation of the CD32a receptor induces the production of pro-inflammatory cytokines, including TNFα and interferons, that are involved into inflammation in systemic lupus erythematosus, Kawasaki disease, Graves’ disease and rheumatoid arthritis. It has been shown that antibacterial activity of platelets is carried out via the CD32a receptor. The study of CD32a expression in people The CD32a receptor is considered a biomarker of cells that are a reservoir of HIV infection. At the present time, however, many questions remain regarding the mechanisms of CD32a expression of on HIV-infected cells and the role of CD32a in the formation of an HIV reservoir and/or development of appropriate resistance. In addition to HIV infection, the significance of FcγR receptors is shown in other infectious diseases, for example, with influenza and dengue virus infections. Better understanding of the CD32a structure and function will help to assess its role in immunopathogenesis of different conditions. This review focuses on the role of CD32a in development of the normal immune response in normal state and various diseases.

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Treatment of ebola and other infectious diseases: melatonin “goes viral”

Melatonin Research ◽

10.32794/mr11250047 ◽

2020 ◽

Vol 3 (1) ◽

pp. 43-57 ◽

Cited By ~ 21

Author(s):

Russel J Reiter ◽

Qiang Ma ◽

Ramaswamy Sharma

Keyword(s):

Mortality Rate ◽

Infectious Diseases ◽

Hemorrhagic Shock ◽

Safety Profile ◽

Ebola Virus ◽

Viral Infections ◽

Virus Disease ◽

Attractive Potential ◽

Potential Treatment

This review summarizes published reports on the utility of melatonin as a treatment for virus-mediated diseases. Of special note are the data related to the role of melatonin in influencing Ebola virus disease. This infection and deadly condition has no effective treatment and the published works documenting the ability of melatonin to attenuate the severity of viral infections generally and Ebola infection specifically are considered. The capacity of melatonin to prevent one of the major complications of an Ebola infection, i.e., the hemorrhagic shock syndrome, which often contributes to the high mortality rate, is noteworthy. Considering the high safety profile of melatonin, the fact that it is easily produced, inexpensive and can be self-administered makes it an attractive potential treatment for Ebola virus pathology.

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Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

Pediatric Reports ◽

10.3390/pediatric13030045 ◽

2021 ◽

Vol 13 (3) ◽

pp. 363-382

Author(s):

Mario Dioguardi ◽

Angela Pia Cazzolla ◽

Claudia Arena ◽

Diego Sovereto ◽

Giorgia Apollonia Caloro ◽

...

Keyword(s):

Innate Immunity ◽

Viral Infections ◽

Respiratory Infections ◽

Viral Disease ◽

Receptor Expression ◽

Virus Infections ◽

Search Terms ◽

Bibliographic Search ◽

Meta Analyses

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

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Role of cannabinoids in various diseases: A review

Current Pharmaceutical Biotechnology ◽

10.2174/1389201023666211223164656 ◽

2021 ◽

Vol 23 ◽

Author(s):

Simran Kaur ◽

Nikita Sharma ◽

Arpita Roy

Keyword(s):

Infectious Diseases ◽

Metabolic Disorders ◽

Viral Infections ◽

Cannabis Sativa ◽

Endocannabinoid System ◽

Psychological Disorders ◽

Bioactive Compound ◽

The Body ◽

Therapeutic Aspect

Background: The plant, Cannabis sativa is heavily explored and researched with many industrial and pharmaceutical applications. The medicinal and therapeutic role of cannabis Sativa has been summarized in the paper, citing its mechanism of action and influence on the human body. Diseases like metabolic disorders, infectious diseases, and psychological disorders pose negative and long-term drastic effects on the body like neurodegeneration and other chronic system failures. Several existing literature has proved its effectiveness against such diseases. Objectives: This review aims to provide an overview of the role of cannabinoids in various diseases like metabolic disorders, infectious diseases, and psychological disorders. Method: Various e-resources like Pubmed, Science Direct, and Google Scholar were thoroughly searched and read to form a well-informed and information-heavy manuscript. Here we tried to summaries the therapeutic aspect of Cannabis sativa and its bioactive compound cannabinoids in various diseases. Result: This review highlights the various constituents which are present in Cannabis sativa, the Endocannabinoid system, and the role of cannabinoids in various diseases Conclusion: Recent research on Cannabis has suggested its role in neurodegenerative diseases, inflammation, sleep disorders, pediatric diseases, and their analgesic nature. Therefore, the authors majorly focus on the therapeutic aspect of Cannabis sativa in various diseases. The focus is also on the endocannabinoid system (ECS) and its role in fighting or preventing bacterial, parasitic, fungal, and viral infections.

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The role of PCSK9 in infectious diseases.

Current Medicinal Chemistry ◽

10.2174/0929867328666210714160343 ◽

2021 ◽

Vol 28 ◽

Author(s):

Laura Magnasco ◽

Chiara Sepulcri ◽

Roberta Maria Antonello ◽

Stefano Di Bella ◽

Laura Labate ◽

...

Keyword(s):

Infectious Diseases ◽

Malaria Infection ◽

Bacterial Infections ◽

Viral Infections ◽

Physiological Role ◽

Protective Role ◽

Loss Of Function ◽

Pcsk9 Inhibition ◽

Sepsis And Septic Shock

Background: In recent years, many aspects of the physiological role of PCSK9 have been elucidated, particularly regarding its role in lipid metabolism, cardiovascular risk, and its role in innate immunity. Increasing evidence is available about the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, and the regulation of host response to bacterial infections, primarily sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity. Objective: This paper aims to review the available published literature on the role of PCSK9 in a wide array of infectious diseases. Conclusion: Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients to treat HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Finally, a loss of function in the PCSK9-encoding gene has been reported to reduce malaria infection mortality.

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Immune deposit and vasculopathy in metabolic-active lung tissues of patients with pulmonary tuberculosis

10.1101/2021.02.09.430558 ◽

2021 ◽

Author(s):

Hui Ma ◽

Lin Wang ◽

Zilu Wen ◽

Xinchun Chen ◽

Haiying Liu ◽

...

Keyword(s):

Gene Expression ◽

Systemic Lupus Erythematosus ◽

Inflammatory Response ◽

Pulmonary Tuberculosis ◽

Autoimmune Diseases ◽

Metabolic Activity ◽

Lupus Erythematosus ◽

Immune Complexes ◽

Systemic Lupus ◽

Dsdna Antibodies

ABSTRACTMetabolic activity in pulmonary lesion is associated with disease severity and relapse risk in tuberculosis. However, the nature of the metabolic activity associated with tuberculosis in humans remains unclear. Previous works indicate that tuberculosis bears resemblance transcriptionally with systemic lupus erythematosus in peripheral blood, except that the plasma cell component was absent in tuberculosis. Here we reported that the missing transcriptional component was present within the metabolic active tissues in the lung of patients with sputum culture-negative tuberculosis, within which increased levels of circulating immune complexes and anti-dsDNA antibodies were found relative to nearby non-metabolic active tissues. Histological examination revealed specific vascular deposition of immune complexes, neutrophil extracellular traps, and vascular necrosis in the metabolic-active tissue. Thus, tuberculosis-initiated metabolic activity was associated with hyperactive antibody responses and vascular pathology, and shared features with systemic lupus erythematosus and other autoimmune diseases. We discussed these observations in the context of earlier literatures demonstrating that similar effects could be induced in humans and animal models by complete freund’s adjuvant, the most potent antibody response inducer ever reported. Our small case series, if verified in a larger size study, might help inform host-directed therapies to alleviate disease progression and augment treatment efficacy.IMPORTANCEIn patients with pulmonary tuberculosis, lung tissues were destroyed by a hyperactive inflammatory response towards M. tuberculosis. The mechanisms underlying the inflammatory response are still poorly understood. Using 18F-FDG avidity as a surrogate marker of inflammation, we have identified that hyper-inflamed tissues possessed features associated with systemic lupus erythematosus: gene expression signatures of plasma cell and immunoglobulins and increased levels of anti-dsDNA antibodies, immune deposits, and vasculopathy. This observation might suggest an explanation to why patients with tuberculosis share more gene expression signatures with autoimmune diseases than infectious diseases and why they are more likely to develop autoimmune diseases. Defining the inflammatory responses at the lesion could help inform host-directed therapies to intervene disease progression or even accelerate cure.

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Stem Cell Therapy and Regenerative Medicine in Autoimmune Diseases

10.5772/intechopen.89749 ◽

2021 ◽

Author(s):

Bhuvaneshwari Sampath ◽

Priyadarshan Kathirvelu ◽

Kavitha Sankaranarayanan

Keyword(s):

Stem Cell ◽

Immune System ◽

Regenerative Medicine ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Autoimmune Condition ◽

Recent Trends

The role of immune system in our body is to defense against the foreign bodies. However, if the immune system fails to recognize self and non-self-cells in our body leads to autoimmune diseases. Widespread autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, and more yet to be added to the list. This chapter discusses about how stem cell-based therapies and advancement of regenerative medicine endow with novel treatment for autoimmune diseases. Furthermore, in detail, specific types of stem cells and their therapeutic approach for each autoimmune condition along with their efficiency to obtain desired results are discussed. Ultimately, this chapter describes the recent trends in treating autoimmune diseases effectively using advanced stem cell research.

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Uracil-Containing Heterodimers of a New Type: Synthesis and Study of Their Anti-Viral Properties

Molecules ◽

10.3390/molecules25153350 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3350

Author(s):

Anna A. Maslova ◽

Elena S. Matyugina ◽

Robert Snoeck ◽

Graciela Andrei ◽

Sergey N. Kochetkov ◽

...

Keyword(s):

Hiv Infection ◽

Reverse Transcriptase ◽

Viral Infections ◽

Virus Infections ◽

Healthy Individuals ◽

Type Synthesis ◽

Hiv Reverse Transcriptase ◽

Reverse Transcriptase Inhibitors ◽

New Type ◽

Nucleoside Inhibitors

Widespread latent herpes viral infections within a population can lead to the development of co-infections in HIV-infected patients. These infections are not particularly dangerous for healthy individuals and often occur with minimal symptoms, but for those who are immunocompromised, these infections can accelerate the acute phase of HIV infection and AIDS. Thus, the idea of designing compounds that could combine activity against HIV and co-infections would seem promising. In that regard, eleven compounds were synthesized that represent conjugates of non-nucleoside HIV reverse transcriptase inhibitors and nucleoside inhibitors of the herpes family viruses with the hope that these novel heterodimers will result in dual activity against HIV and concomitant herpes virus infections.

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Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms

Viruses ◽

10.3390/v11080762 ◽

2019 ◽

Vol 11 (8) ◽

pp. 762 ◽

Cited By ~ 38

Author(s):

Maria K. Smatti ◽

Farhan S. Cyprian ◽

Gheyath K. Nasrallah ◽

Asmaa A. Al Thani ◽

Ruba O. Almishal ◽

...

Keyword(s):

Immune Responses ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Influenza A ◽

Molecular Mechanisms ◽

Viral Infections ◽

Molecular Mimicry ◽

Experimental Studies ◽

Onset Time ◽

Protective Effects

For a long time, viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), herpetic stromal keratitis (HSK), celiac disease (CD), and multiple sclerosis (MS). Best examples of viral infections that have been proposed to modulate the induction and development of autoimmune diseases are the infections with enteric viruses such as Coxsackie B virus (CVB) and rotavirus, as well as influenza A viruses (IAV), and herpesviruses. Other viruses that have been studied in this context include, measles, mumps, and rubella. Epidemiological studies in humans and experimental studies in animal have shown that viral infections can induce or protect from autoimmunopathologies depending on several factors including genetic background, host-elicited immune responses, type of virus strain, viral load, and the onset time of infection. Still, data delineating the clear mechanistic interaction between the virus and the immune system to induce autoreactivity are scarce. Available data indicate that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells. Contrarily, the protective effects can be achieved via regulatory immune responses which lead to the suppression of autoimmune phenomena. Therefore, a better understanding of the immune-related molecular processes in virus-induced autoimmunity is warranted. Here we provide an overview of the current understanding of viral-induced autoimmunity and the mechanisms that are associated with this phenomenon.

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Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections

Vaccines ◽

10.3390/vaccines8030517 ◽

2020 ◽

Vol 8 (3) ◽

pp. 517 ◽

Cited By ~ 3

Author(s):

Bapi Pahar ◽

Stefania Madonna ◽

Arpita Das ◽

Cristina Albanesi ◽

Giampiero Girolomoni

Keyword(s):

Lupus Erythematosus ◽

Cytokine Production ◽

Viral Infections ◽

Normal Skin ◽

Epidermal Keratinocytes ◽

New Approach ◽

Virus Dissemination ◽

Monocytes And Macrophages ◽

Progression Of Disease

Antimicrobial peptides (AMPs) are produced by neutrophils, monocytes, and macrophages, as well as epithelial cells, and are an essential component of innate immunity system against infection, including several viral infections. AMPs, in particular the cathelicidin LL-37, also exert numerous immunomodulatory activities by inducing cytokine production and attracting and regulating the activity of immune cells. AMPs are scarcely expressed in normal skin, but their expression increases when skin is injured by external factors, such as trauma, inflammation, or infection. LL-37 complexed to self-DNA acts as autoantigen in psoriasis and lupus erythematosus (LE), where it also induces production of interferon by plasmocytoid dendritic cells and thus initiates a cascade of autocrine and paracrine processes, leading to a disease state. In these disorders, epidermal keratinocytes express high amounts of AMPs, which can lead to uncontrolled inflammation. Similarly, LL-37 had several favorable and unfavorable roles in virus replication and disease pathogenesis. Targeting the antiviral and immunomodulatory functions of LL-37 opens a new approach to limit virus dissemination and the progression of disease.

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HIV Infection and Specific Mucosal Immunity

Advances in Dental Research ◽

10.1177/0022034511400222 ◽

2011 ◽

Vol 23 (1) ◽

pp. 142-151 ◽

Cited By ~ 3

Author(s):

S.J. Challacombe ◽

P.L. Fidel ◽

S. Tugizov ◽

L. Tao ◽

S.M. Wahl

Keyword(s):

Breast Milk ◽

Hiv Infection ◽

Mucosal Immunity ◽

Neutralizing Antibodies ◽

Viral Infections ◽

Immunoglobulin A ◽

Hiv Infections ◽

Mucosal Vaccine ◽

Lymphoid Tissues

Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues—namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.

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