Research progress on immunomodulatory properties of periodontal ligament stem cells / 口腔疾病防治

@#Periodontal ligament stem cells (PDLSCs) have the potential for multidirectional differentiation and are the preferred seed cells for periodontal tissue regeneration. In recent years, a large number of studies have confirmed that PDLSCs also possess broad immunomodulatory properties. Therefore, in-depth exploration of their specific molecular mechanisms is of great significance for the treatment of periodontitis. The aim of this paper is to summarize the research progress on the regulation of PDLSCs on various immune cells and the effect of the inflammatory environment on the immune characteristics of PDLSCs to provide an important theoretical basis for the allotransplantation of PDLSCs and improve the therapeutic effect of periodontal tissue regeneration. Studies have shown that PDLSCs possess a certain degree of immunosuppressive effect on both innate and acquired immune cells, and inflammatory stimulation may lead to the impairment of the immunoregulatory properties of PDLSCs. However, current studies are mainly limited to in vitro cell tests and lack in-depth studies on the immunomodulatory effects of PDLSCs in vivo. In vivo studies based on cell lineage tracing and conditional gene knockout technology may become the main directions for future research.

Pathogenesis of Diabetes from Theory of Spleen Deficiency Causing Diabetes Based on Intestinal Innate Immunity / 中国实验方剂学杂志

In western medicine， the small intestine anatomically belongs to the digestive system and is also an important immune organ of the body. The innate immune system of the small intestine consists of a tissue barrier， innate immune cells， and innate immune molecules. The dysfunction of any part can cause metabolic disorders and eventually lead to diabetes. In the pathogenesis of diabetes， traditional Chinese medicine （TCM） has the theory of ''spleen deficiency causing diabetes''， which points out that the impaired spleen function results in inadequate transformation， impaired essence spread， and turbidity by essence accumulation， which is the core pathological link of blood glucose metabolism disorder in diabetes. In terms of the relationship between the small intestine and the spleen， the theory of TCM holds that the small intestine is located in the abdomen and the abdomen is dominated by the spleen. The digestion， absorption， and endocrine functions of the small intestine are also similar to the functions of spleen in governing movement and transformation and spreading essence by virtue of spleen Qi. Therefore， the anatomical and physiological functions of the small intestine in western medicine are closely related to the spleen in TCM. At the same time， the spleen is closely related to the innate immune function of the small intestine in TCM. The spleen participates in the generation and distribution of defense Qi， and the process of defense Qi playing the external function is similar to the process of the activation of the innate immune response. The spleen is also an important organ involved in fluid metabolism， which can cooperate with the lung and kidney to timely remove turbid fluid from the body. It can also work with the stomach as the hub of Qi ascending and descending and regulate the physiological activities of "clear Yang" and "turbid Yin"， so as to ensure the homeostasis of the internal environment of the body， which is the basis for maintaining the normal function of the innate immunity of the small intestine. Therefore， taking "spleen deficiency causing diabetes" as a bridge， the theory of TCM and western medicine were combined to explain the relationship between small intestinal innate immunity imbalance and the pathogenesis of diabetes from the perspective of TCM， which is helpful to understand the pathogenesis of diabetes in a deeper level and also provide a new perspective and new way for the prevention and treatment of this disease with TCM.

Research progress on the role and changes of natural killer cells in sepsis / 中国小儿急救医学

Sepsis is the organ dysfunction caused by infection.It is one of the most common critical diseases in clinic.Its morbidity and mortality are increasing year by year，which has seriously threatened human health.Innate immunity is the first line of defense against pathogens.Nature killer（NK）cells are important cells involved in the regulation of innate immunity in sepsis，and can play an important role on the progression of sepsis by secreting cytokines，inducing apoptosis and mediating cytotoxic effects.It has been found that the changes of NK cells in the early stage of sepsis are related to the prognosis of the disease.Therefore，further study on the role of NK cells in sepsis can provide a new idea for the clinical diagnosis and treatment of sepsis，and contribute to the early identification of sepsis and the improvement of prognosis.This review summarized the role and changes of NK cell in sepsis.

Initiation and maintenance of acquired immunity in dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

Dry eye(DE)is a multifactorial ocular surface disorder arising from numerous pathologies. The pathogenesis of DE includes immune inflammation, oxidative stress, changes in tear film composition, corneal nerve abnormalities, and meibomian gland dysfunction. Among them, the immune inflammatory response is the most crucial in the pathogenesis of DE, which is regulated by both innate and acquired immune responses on the ocular surface. Multiple environmental stresses trigger the ocular surface innate immune response leading to corneal epithelial cell damage and inflammation and activate acquired immunity to participate in the ocular surface immune inflammatory response. Currently, multiple immune cells and inflammatory factors have been shown to be involved in the occurrence and development of DE. This article reviewed the immune progress and focused on the initiation and maintenance of acquired immunity in DE. Through the analysis of the latest viewpoints and research hot spots, we systematically introduced the immunomodulating mechanism underlying the mechanisms of the pathogenesis of DE and provided references for the prevention and treatment of DE.

The role of innate immunity in diabetic nephropathy and their therapeutic consequences / 药物分析学报

Diabetic nephropathy(DN)is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide.A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN,ultimately resulting in renal failure.Mounting evidence suggests that immunological and inflammatory factors are crucial for the develop-ment of DN.Therefore,the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation.Toll-like receptors(TLRs)are an important group of re-ceptors that identify patterns and activate immune responses and inflammation.Meanwhile,inflam-matory responses in the liver,pancreatic islets,and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines.Moreover,the activation of the complement cascade can be triggered by glycated proteins.This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction,ultimately leading to renal failure.This re-view also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.

Mechanism of Helicobacter pylori metabolites antagonizing host innate immunity / 中国免疫学杂志

Objective:To investigate potential mechanism of Helicobacter pylori metabolites antagonizing host innate immunity.Methods:RNA sequencing and pathway enrichment analysis were used to analyze only LPS-stimulated gastric mucosal cells GES-1,GES-1 cells co-treated with LPS and Helicobacter pylori culture supernatant,and untreated GES-1 cells.The culture supernatant of He-licobacter pylori was filtered by a 3KD ultrafiltration tube,and the filtered filtrate(metabolite part)and the retained solution(protein part)were treated with LPS-stimulated GES-1 cells to detect activity of NF-κB pathway,phosphorylation level of NF-κB,secretion levels of NF-κB pathway effectors TNF-α,IL-6 and IL-8.Identification of key metabolites by untargeted metabolic mass spectrometry.Results:Compared with GES-1 cells stimulated only by LPS,after co-treated with LPS and Helicobacter pylori culture supernatant,expression levels of various genes were regulated and tended to the level of GES-1 in untreated gastric mucosal cells,mainly in the NF-κB pathway.After co-treatment with LPS and culture supernatant of Helicobacter pylori,activity of NF-κB pathway was inhibited(P<0.05).Helicobacter pylori metabolites could inhibit the activity of NF-κB pathway,inhibit phosphorylation of NF-κB,and inhibit the secretion of NF-κB pathway effectors TNF-α,IL-6 and IL-8(P<0.05).1,5 and 25 μmol/L of Helicobacter pylori metabolite 2-D-Glu-copyranose(2DG)treatment inhibited activity of NF-κB pathway and phosphorylation of NF-κB in GES-1 cells,and secretion of NF-κB pathway effectors TNF-α,IL-6 and IL-8 were inhibited(P<0.05).After 2DG treatment,activity of NF-κB in GES-1 cells with TLR3,TLR4,TLR5,TLR6,TLR7,TLR8,TLR9 and TLR10 knockout were significantly decreased(P<0.05);while there was no significant changes in activity of NF-κB in TLR1 and TLR2 knockout GES-1 cells.Both TLR1 and TLR2 interactions were attenuated in GES-1 cells after 2DG treatment.Molecular docking showed that 2DG could bind to TLR2 amino acid disabled R321,K347 and F349,the binding energy was-12 kcal/mol.TLR2 wild-type and mutant plasmids(R321K,K347R,F349A)were constructed,and TLR2-knockout GES-1 cells were respectively transfected.It was found that 2DG treatment did not reduce NF-κB activity in GES-1 cells transfected with TLR2 mutant.Conclusion:Helicobacter pylori metabolite 2DG can interact with TLR2,reduce the formation of het-erodimers between TLR2 and TLR1,and inhibit the activity of innate immune NF-κB pathway.

La Viabilidad y Funcionalidad de Leucocitos Humanos en presencia de un Extracto Hidro-alcohólico de E. coca / The Viability and Functionality of Human Leukocytes in the presence of a Hydro-alcoholic Extract of E. coca.

Introducción : Para estudiar el efecto de cualquier producto natural, aunque sea de uso habitual de la medicina tradicional, es necesario establecer previamente los márgenes de seguridad para su utilización en humanos. En el caso de Erythroxylum coca, para trazar sus perspectivas de uso como fitofármaco o de producto industrial, es necesario conocer si tiene algún grado de toxicidad o si es completamente inocuo, no obstante, su larga tradición de consumo. Objetivo : Explorar el efecto de un extracto hidro-alcohólico de E. coca sobre granulocitos y mononucleares de voluntarios donadores humanos, en condiciones de cultivo celular. Se examinó, por un lado, el efecto sobre la viabilidad celular y la actividad del sistema mitocondrial/citoplasmático de óxido-reductasas y, por otra parte, se exploró su efecto sobre la funcionalidad celular a través de la determinación de la capacidad fagocítica, la quimiotaxis, la endocitosis y la actividad microbicida, en el ámbito de la inmunidad innata, y la capacidad de liberación o estimulación de citoquinas en el ámbito de la respuesta inflamatoria. Materiales y Métodos : Se evaluó la viabilidad por Azul Tripan, la actividad de oxido reductasas por reducción de MTT, la capacidad endocitica de levaduras, quimiotaxis en gel de agarosa hacia el péptido Fmlp y actividad microbicida sobre S.aureus. Las liberaciones de citoquinas se evaluaron por ELISA. Resultados : Se encontró que a las dosis equivalentes a la del consumo habitual humano, los leucocitos conservan su viabilidad (0,13µg/ml), la que se mantiene hasta dosis relativamente altas (130µg/ml). En esta franja de seguridad se encontró que E. coca no altera la capacidad de las enzimas mitocondriales y citoplasmáticas de óxido- reducción, al contrario, en dosis bajas es capaz de estimular dicha actividad. La actividad quimiotactica no es afectada por el extracto hidroalcoholico de coca por el contrario a dosis intermedias esta actividad se eleva de manera ostensible. La capacidad endocitica no se ve afectada y por el contrario se pudo observar un estímulo de la misma; en la actividad microbicida no existe cambios significativos. Conclusiones : Se concluye que, este producto a las dosis equivalentes a las recomendadas por la medicina tradicional no tiene efectos deletéreos sobre la viabilidad y funcionalidad de los leucocitos humanos. En lo que respecta a la actividad del extracto sobre la producción de citoquinas, se encontró que E. coca tiene efecto de estimulación en la liberación de TNF e inhibición de IL-10 modulando así mayor actividad proinflamatoria.

Introduction : In order to study the effect of any natural product, even if it is commonly used in traditional medicine, it is necessary to previously establish the safety margins for its use in humans. In the case of Erythroxylum coca, in order to trace its prospects of use as a phytopharmaceutical or industrial product, it is necessary to know if it has any degree of toxicity or if it is completely innocuous, despite its long tradition of consumption. Objective : To explore the effect of a hydro-alcoholic extract of E. coca on granulocytes and mononuclear cells of human donor volunteers, under cell culture conditions. We examined, on the one hand, the effect on cell viability and the activity of the mitochondrial/cytoplasmic oxidoreductase system and, on the other hand, it was explored its effect on cellular functionality through the determination of phagocytic capacity, chemotaxis, endocytosis and microbicidal activity, in the field of innate immunity, and the capacity of release or stimulation of cytokines in the field of inflammatory response. Materials and Methods : Viability by Trypan Blue, oxidoreductase activity by MTT reduction, endocytic capacity of yeast, chemotaxis in agarose gel towards Fmlp peptide and microbicidal activity on S.aureus were evaluated. Cytokine release was evaluated by ELISA. Results : It was found that at doses equivalent to the usual human consumption, leukocytes retain their viability (0.13µg/ml), which is maintained up to relatively high doses (130µg/ml). In this safety range it was found that E. coca does not alter the capacity of mitochondrial and cytoplasmic oxidation-reduction enzymes, on the contrary, at low doses it is able to stimulate such activity. The chemotactic activity is not affected by the hydroalcoholic extract of coca, on the contrary, at intermediate doses this activity is ostensibly elevated. The endocytic capacity is not affected and, on the contrary, a stimulus of the same was observed; in the microbicidal activity there are no significant changes. Conclusions : It is concluded that this product, at doses equivalent to those recommended by traditional medicine, has no deleterious effects on the viability and functionality of human leukocytes. Regarding the activity of the extract on the production of cytokines, it was found that E. coca has a stimulating effect on the release of TNF and inhibition of IL-10, thus modulating greater proinflammatory activity.

Research progress of interaction between peste des petits ruminants virus and host cells / 中国生物制品学杂志

@#Peste des petits ruminants(PPR)is a highly contagious disease with high mortality which is caused by peste des petits ruminants virus(PPRV)infection and leads to enormous economic losses for sheep husbandry both at home and abroad. The knowledge of interactions between PPRV and host cells is the basis of understanding of the pathogenesis and the prerequisite of disease prevention and control. This paper reviews the studies on the activation of host innate immune response by PPRV infection,the immune evasion of PPRV mediated by viral protein products,and the induction of apoptosis,autophagy and inflammasome resistance to virus,which provides a reference for further discussion on the immune evasion of PPRV and the key nodes involved in the interaction between PPRV and the host,thus providing theoretical guidance for effective prevention and control of PPR transmission.

Research progress on the role of type II innate lymphoid cells in liver diseases / 中华肝脏病杂志

Type II innate lymphoid cell (ILC2) is a newly identified innate immunological cell that belongs to the lymphocyte lineage in cell morphology, resides in the body's mucosal tissues, and has the dual functions of innate and adaptive immunity to promote tissue remodeling and repair after injury. Additionally, it is involved in the occurrence and development of a variety of liver diseases and plays an important role in maintaining the immunological homeostasis of the liver region. This article reviews the differentiation, development, and biological functions of ILC2, with particular attention to the research progress in liver diseases.

Potentiating effect and mechanism of extract of Jingfang Granules on activation of macrophages / 中国中药杂志

This study aimed to explore the potentiating effect and mechanism of the extract of Jingfang Granules(JFG) on the activation of macrophages. The RAW264.7 cells were treated with JFG extract and then stimulated by multiple agents. Subsequently, mRNA was extracted, and reverse transcription-polymerase chain reaction(RT-PCR) was used to measure the mRNA transcription of multiple cytokines in RAW264.7 cells. The levels of cytokines in the cell supernatant were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the intracellular proteins were extracted and the activation of signaling pathways was determined by Western blot. The results showed that JFG extract alone could not promote or slightly promote the mRNA transcription of TNF-α, IL-6, IL-1β, MIP-1α, MCP-1, CCL5, IP-10, and IFN-β, and significantly enhance the mRNA transcription of these cytokines in RAW264.7 cells induced by R848 and CpG in a dose-dependent manner. Furthermore, JFG extract also potentiated the secretion of TNF-α, IL-6, MCP-1, and IFN-β by RAW264.7 cells stimulated with R848 and CpG. As revealed by mechanism analysis, JFG extract enhanced the phosphorylation of p38, ERK1/2, IRF3, STAT1, and STAT3 in RAW264.7 cells induced by CpG. The findings of this study indicate that JFG extract can selectively potentiate the activation of macrophages induced by R848 and CpG, which may be attributed to the promotion of the activation of MAPKs, IRF3, and STAT1/3 signaling pathways.

Advances in the study of congenital immune mechanisms mediated by modifiable cardiovascular risk factors for atherosclerosis / 中国胸心血管外科临床杂志

@#Obesity, sleep disorders, psychological stress, sedentary are modifiable cardiovascular risk factors. There is growing evidence that these risk factors may accelerate the chronic inflammatory process of atherosclerosis and lead to myocardial infarction. Studies on the role of immune cells and their related immune mechanisms in atherosclerosis have shown that the above modifiable risk factors can affect the hematopoiesis of the bone marrow system, affect the production of immune cells and phenotypes, and then affect the progress of atherosclerosis. This review will focus on the effects of modifiable cardiovascular risk factors on the progression of atherosclerosis through the role of the innate immune system.

Advances in the role of innate immunity in Epstein-Barr virus infection / 国际儿科学杂志

Epstein-Barr virus(EBV)is a double-stranded DNA herpes virus that is universally susceptible to human populations worldwide.It mainly infects B cells and epithelial cells and has the characteristics of incubation and transformation.The innate immune response is the first line of defense against EBV.In particular, the immune response of type Ⅰ interferons and the direct cell-killing effects of innate cytotoxic lymphocyte are essential for initial control of viral infection and subsequent activation of adaptive immune responses.There is a delicate balance between innate immune response and immune escape of EBV, and the breakdown of the balance is related to the occurrence and prognosis of EBV-related diseases.A better understanding of this balance mechanism will guide the prevention and targeted therapy of EBV-related diseases.This article reviews the role of innate immune cells(epithelial cells, mononuclear/dendritic cells, NK cells, γδT cells, NKT cells)and type Ⅰ interferon in EBV infection and the immune escape mechanism of EBV.

Progress in autophagy regulated by hepatitis B virus infection / 中华微生物学和免疫学杂志

Hepatitis B virus (HBV) infection can cause a series of severe liver diseases such as chronic hepatitis B, liver cirrhosis and hepatocellular carcinoma, remaining one of most serious worldwide public health problems. Autophagy is a conserved lysosome-dependent degradation pathway in eukaryotic cells and plays a critical role in host innate immune response. Multiple processes in the life cycle of HBV, including viral replication, maturation and secretion, are closely related to autophagy. Autophagy can regulate the assemble, envelopment and secretion of HBV in human hepatocytes and participate in innate and adaptive immune responses to clear HBV. HBV induces strong autophagy in human hepatocytes and escapes autophagic degradation through certain mechanisms. This review summarized the progress in autophagy and autophagic degradation regulated by HBV infection, hoping to provide a theoretical reference for further understanding the mechanism of autophagy regulated by HBV infection and developing novel strategies for anti-HBV therapy.

Counteractive effect of mouse dermal fibroblasts during their adipogenic differentiation against Staphylococcus aureus infection and its mechanisms / 中华皮肤科杂志

Objective:To investigate the counteractive effect of mouse dermal fibroblasts (MdFBs) during their adipogenic differentiation against Staphylococcus aureus infection, and to explore its mechanisms. Methods:MdFBs were obtained from newborn C57BL/6 mice, and their adipogenic differentiation was induced by culture in an adipogenic medium for 48 hours. Real-time fluorescence-based quantitative PCR (RT-PCR) was performed to determine the mRNA expression of cathelicidin antimicrobial peptide (CAMP) on days 0-6 during the adipogenic differentiation of MdFBs, and Western blot analysis to determine the protein expression of CAMP in the culture supernatant of MdFBs during their adipogenic differentiation. MdFBs were divided into 4 groups: co-stimulation group stimulated by S. aureus suspensions and cultured in an adipogenic medium, adipogenic control group cultured in an adipogenic medium, S. aureus-stimulation group stimulated by S. aureus suspensions and cultured in a common medium, and control group stimulated by phosphate-buffered saline and cultured in a common medium; Western blot analysis and RT-PCR were conducted to determine the protein and mRNA expression of CAMP. S. aureus (5 × 10 4 CFU/ml) was cultured with the culture supernatant of MdFBs after 5-day adipogenic differentiation (adipogenic group), and the growth activity was evaluated every 2 hours during 10 - 24 hours after the start of co-culture; S. aureus cultured with the culture supernatant of MdFBs in a common medium served as the normal control group, and that cultured with cell-free culture supernatant served as the negative control group. Differences between groups were assessed using unpaired t-test or analysis of variance. Results:Significant differences were observed in the relative mRNA expression of CAMP among different time points (days 0, 1, 2, 4, and 6) during the adipogenic differentiation of MdFBs (1.14 ± 0.74, 68.04 ± 12.72, 683.12 ± 38.06, 1 390.68 ± 226.21, 454.57 ± 204.12, F = 50.08, P < 0.001) ; the CAMP mRNA expression was significantly higher on days 1, 2, 4, and 6 than on day 0 ( t = 9.09, 31.03, 10.63, 3.85, respectively, all P < 0.05), and showed an initial rise and subsequent fall during days 0 - 6. The CAMP protein expression in the culture supernatant of MdFBs peaked on days 2-5 and subsequently decreased. Significant differences were observed in the mRNA and protein expression of CAMP among the control group, S. aureus-stimulation group, adipogenic control group and co-stimulation group (mRNA: 0.08 ± 0.02, 0.38 ± 0.10, 0.49 ± 0.11, 0.80 ± 0.03, respectively, F = 43.25, P < 0.05; protein: 0.433 ± 0.176, 0.574 ± 0.176, 1.007 ± 0.176, 1.217 ± 0.176, respectively, F = 46.79, P < 0.05), and the relative mRNA and protein expression of CAMP was significantly higher in the co-stimulation group than in the adipogenic control group, S. aureus-stimulation group and control group (all P < 0.05). At 10 hours during culture, the growth activity of S. aureus was significantly lower in the adipogenic group (0.053 ± 0.015) than in the normal control group and negative control group (0.109 ± 0.015, 0.106 ± 0.015, t = 11.30, 13.26, respectively, both P < 0.05) ; during 10 - 24 hours, the growth activity of S. aureus also showed a significant decrease in the adipogenic group compared with the normal control group and negative control group (all P < 0.05) . Conclusion:MdFBs secreted CAMP during the adipogenic differentiation, and could inhibit the proliferation of S. aureus.

Role of innate immune cells in host immune responses against Aspergillus fumigatus / 中华微生物学和免疫学杂志

Aspergillus fumigatus ( A. fumigatus) is an environmental filamentous fungus and an opportunistic pathogen that can cause chronic and invasive aspergillosis. The development of aspergillosis is the result of the interaction between the host and the pathogen, and the symptoms of A. fumigatus infection varied in patients with different immune status. The host innate immune response to inhaled fungal spores is a key determinant of the development of aspergillosis. This review focused on the role of innate immune cells including macrophages, neutrophils, natural killer cells, natural killer T cells and mast cells in host defense against A. fumigatus, aiming to provide reference for further research on the pathogenesis, clinical prevention and treatment of aspergillosis.

Research progress in the role of E3 ubiquitin ligases in viral infection / 中华微生物学和免疫学杂志

Ubiquitination modifications are a kind of post-translational modifications of proteins widely found in eukaryotes and involved in a variety of biological activities. E3 ubiquitin ligases are an important component of the ubiquitin system, with the function of specific recognition of substrate proteins and mediation of different types of ubiquitination modifications. They can regulate the function and life time of substrate proteins. Recent studies have shown that E3 ubiquitin ligases are widely involved in the regulation of the host innate immune response and can directly or indirectly influence viral infection. Moreover, viruses are able to encode or hijack E3 ubiquitin ligases in their long-term evolution, allowing them to play an important role in viral infection and replication cycle. This paper reviewed the progress in the mechanisms of E3 ubiquitin ligases in innate immune responses and viral infection in recent years.

Antimicrobial Activity and Working Mechanism of Human Ribonuclease A Superfamily / 中国生物化学与分子生物学报

Human RNase A (human RNase A) superfamily contains 13 members (RNase 1~RNase 13) with different biological activities. In addition to the conserved catalytic sequence, its protein structure also has a significant diversity of sequences, which determines that human ribonuclease A can exert biological functions other than ribonuclease activity. Human RNase A superfamily members are expressed in various immune cells such as eosinophils, neutrophils, monocytes, and macrophages and can be secreted to exert various biological functions, including anti-microbial activity, promote host defense, participate in angiogenesis and sperm maturation, etc. Some members of the human ribonuclease A superfamily can exert antimicrobial and antiparasitic activities through direct actions such as hydrolysis of viral RNA, inhibition of viral replication, destruction of bacterial cell walls, promotion of microbial aggregation, damage to parasitic cell membranes and mitochondrial membranes, and indirect actions mediated by host innate immune cells, thereby participating in host defense. This article reviews the antimicrobial (including viruses, bacteria, and fungi) and antiparasitic activities of human ribonuclease A and their mechanisms of action. It also prospects the prospects of human ribonuclease A as an active antimicrobial substance and innate immune molecule for the treatment of severe and drug-resistant microbial infections.

In vitro immunogenic profile of recombinant SARS-CoV2 S1-RBD peptide in murine macrophage and microglial cells

BACKGROUND The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can infect common mice inducing significant pathological lung lesions and inflammatory responses. This substantially mimics coronavirus disease 19 (COVID-19) infection and pathogenesis in humans. OBJECTIVES To characterise the effects of recombinant SARS-CoV-2 S1 receptor-binding domain (RBD) peptide in murine macrophage and microglial cells' immune activation compared with classical PAMPs in vitro. METHODS Murine RAW 264.7 macrophages and BV2 microglial cells were exposed to increasing concentrations of the RBD peptide (0.01, 0.05, and 0.1 µg/mL), Lipopolysaccharide (LPS) and Poly(I:C) and evaluated after two and 24 h for significant markers of macrophage activation. We determined the effects of RBD peptide on cell viability, cleaved caspase 3 expressions, and nuclear morphometry analysis. FINDINGS In RAW cells, RBD peptide was cytotoxic, but not for BV2 cells. RAW cells presented increased arginase activity and IL-10 production; however, BV2 cells expressed iNOS and IL-6 after RBD peptide exposure. In addition, RAW cells increased cleaved-caspase-3, apoptosis, and mitotic catastrophe after RBD peptide stimulation but not BV2 cells. CONCLUSION RBD peptide exposure has different effects depending on the cell line, exposure time, and concentration. This study brings new evidence about the immunogenic profile of RBD in macrophage and microglial cells, advancing the understanding of SARS-Cov2 immuno- and neuropathology.

A short history of innate immunity

Innate immunity refers to the mechanisms responsible for the first line of defense against pathogens, cancer cells and toxins. The innate immune system is also responsible for the initial activation of the body's specific immune response (adaptive immunity). Innate immunity was studied and further developed in parallel with adaptive immunity beginning in the first half of the 19th century and has been gaining increasing importance to our understanding of health and disease. In the present overview, we describe the main findings and ideas that contributed to the development of innate immunity as a continually expanding branch of modern immunology. We start with the toxicological studies by Von Haller and Magendie, in the late 18th and early 19th centuries, and continue with the discoveries in invertebrate immunity that supported the discovery and characterization of lipopolysaccharide (LPS) and pattern recognition receptors that led to the development of the pattern recognition and danger theory.

Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro / Efeitos das redes extracelulares dos neutrófilos durante a infecção in vitro pelo vírus sincicial respiratório

Abstract The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5-16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.

Resumo O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,5-16 μg/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios semelhantes àqueles induzidos pelo vírus em células não tratadas, indicando danos citotóxicos e deletérios. Nossos resultados corroboram achados relatados anteriormente de que as NETs contribuem para a imunopatologia desenvolvida por pacientes infectados com hRSV.