scholarly journals Transcriptome Analysis of Host Inflammatory Responses to the Ectoparasitic Mite Sarcoptes scabiei var. hominis

2021 ◽  
Vol 12 ◽  
Author(s):  
Huma Shehwana ◽  
Sadaf Ijaz ◽  
Abeera Fatima ◽  
Shelley Walton ◽  
Zafar Iqbal Sheikh ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Skin ◽  
Drug Targets ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Clinical Manifestations ◽  
Disease Process ◽  
Sarcoptes Scabiei ◽  
Immunological Responses ◽  
Skin Biopsies

Scabies, a human skin infestation caused by the ectoparasitic mite Sarcoptes scabiei var. hominis, affects more than 200 million people globally. The prevailing knowledge of the disease process and host immune response mechanisms is limited. A better understanding of the host-parasite relationship is essential for the identification of novel vaccine and drug targets. Here we aimed to interrogate the transcriptomic profiles of mite-infested human skin biopsies with clinical manifestations of ordinary scabies subjects (“OS”; n = 05) and subjects naive to scabies (“control”; n = 03) using RNASeq data analysis. A combined clustering, network, and pathway mapping approach enabled us to identify key signaling events in the host immune and pro-inflammatory responses to S. scabiei infestation. The clustering patterns showed various differentially expressed genes including inflammatory responses and innate immunity genes (DEFB4A, IL-19, CXCL8, CSF3, SERPINB4, S100A7A, HRNR) and notably upregulation of the JAK-STAT pathway in scabies-infested samples. Mite-infested human skin biopsies (GSE178563) were compared with an ex-vivo porcine infested model (E-MTAB-6433) and human skin equivalents (GSE48459). Marked enrichment of immune response pathways (JAK-STAT signaling, IL-4 and IL-13 pathway, and Toll receptor cascade), chemokine ligands and receptors (CCL17, CCL18, CCL3L1, CCL3L3, CCR7), and cytokines (IL-13 and IL-20) were observed. Additionally, genes known for their role in psoriasis and atopic dermatitis were upregulated, e.g., IL-19. The detailed transcriptomic profile has provided an insight into molecular functions, biological processes, and immunological responses and increased our understanding about transcriptomic regulation of scabies in human.

scholarly journals Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus

2012 ◽  
Vol 20 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Feng Qian ◽  
Christopher R. Bolen ◽  
Chunxia Jing ◽  
Xiaomei Wang ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
The United States ◽  
Toll Like Receptor

ABSTRACTHepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States, with the majority of patients becoming chronically infected and a subset (20%) progressing to cirrhosis and hepatocellular carcinoma. Individual variations in immune responses may help define successful resistance to infection with HCV. We have compared the immune response in primary macrophages from patients who have spontaneously cleared HCV (viral load negative [VL−],n= 37) to that of primary macrophages from HCV genotype 1 chronically infected (VL+) subjects (n= 32) and found that macrophages from VL− subjects have an elevated baseline expression of Toll-like receptor 3 (TLR3). Macrophages from HCV patients were stimulatedex vivothrough the TLR3 pathway and assessed using gene expression arrays and pathway analysis. We found elevated TLR3 response genes and pathway activity from VL− subjects. Furthermore, macrophages from VL− subjects showed higher production of beta interferon (IFN-β) and related IFN response genes by quantitative PCR (Q-PCR) and increased phosphorylation of STAT-1 by immunoblotting. Analysis of polymorphisms in TLR3 revealed a significant association of intronic TLR3 polymorphism (rs13126816) with the clearance of HCV and the expression of TLR3. Of note, peripheral blood mononuclear cells (PBMCs) from the same donors showed opposite changes in gene expression, suggesting ongoing inflammatory responses in PBMCs from VL+ HCV patients. Our results suggest that an elevated innate immune response enhances HCV clearance mechanisms and may offer a potential therapeutic approach to increase viral clearance.

scholarly journals Covid-19 dan Koinfeksi Penyakit Parasit

2020 ◽  
Vol 7 (1A) ◽  
pp. 298-303
Author(s):  
Reqgi First Trasia
Keyword(s):  
Immune Response ◽  
Poor Prognosis ◽  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Clinical Impact ◽  
Parasitic Infections ◽  
Parasitic Diseases ◽  
Proinflammatory Response ◽  
Intestinal Worms ◽  
Endemic Areas

LATAR BELAKANG: Kondisi pandemi, kasus Covid-19 semakin meningkat, manifestasi klinis seperti demam, batuk, diare, muntah, sakit kepala, mialgia dan kelelahan, mungkin sulit untuk membedakan COVID-19 dari spektrum penyakit dengan manifestasi serupa, seperti malaria dan cacingan, terutama di daerah endemik. Di Indonesia belum ada artikel yang membahas Covid-19 dengan koinfeksi malaria dan cacing. TUJUAN: Tujuan penulisan ini adalah menelaah dampak klinis infeksi Covid-19 dengan komorbid infeksi parasit yaitu malaria dan kecacingan. METODE: Penelusuran kepustakaan 154 jurnal, terdapat 4 jurnal yang relevan. DISKUSI: Manifestasi klinis malaria yang parah terjadi karena respon proinflamasi yang meningkat, hal yang sama terjadi dalam banyak kasus COVID-19. Koinfeksi Malaria dan COVID-19 dapat menyebabkan respons pro-inflamasi yang berlebihan, manifestasi klinis lebih parah dan prognosis buruk. Berdasarkan imunopatogenitas dari infeksi cacing di daerah endemis, dikhawatirkan hal tersebut akan meningkatkan keparahan gejala Covid-19 pada pasien dengan koinfeksi cacing. KESIMPULAN: Pada kasus Covid-19 yang diikuti dengan koinfeksi malaria menunjukkan keparahan manifestasi klinis akibat peningkatan respon inflamasi. Diduga bahwa respon imun hospes terhadap cacing akan memberikan dampak klinis yang lebih berat pada kasus Covid-19. Kata kunci: Covid-19, koinfeksi, malaria, cacingan, penyakit parasit   BACKGROUND: The condition of the Covid-19 pandemic where the number of cases is increasing. Clinical manifestations such as fever, cough, diarrhea, vomiting, headache, myalgia and fatigue, it may be difficult to distinguish COVID-19 from the spectrum of diseases with similar manifestations, such as malaria and intestinal worms, especially in endemic areas. Indonesia there are no articles discussing Covid-19 with malaria and worm coinfection. OBJECTIVE: The purpose this article is to review the clinical impact of Covid-19 infection with comorbid parasitic infections, in this case malaria and worms. METHOD: Search the literature of 154 journals, there are 4 journals that are relevant DISCUSSION: The severe manifestations of malaria occur because of an increased proinflammatory response, the same thing happens in many cases of COVID-19. Malaria coinfection and COVID-19 can then cause excessive pro-inflammatory responses, severe manifestations and a poor prognosis. In addition, based on immunopathogenicity from worm infections in endemic areas, it is feared that this will increase the severity of Covid-19 symptoms in patients with worm co-infection. CONCLUSION: In the case of Covid-19 followed by co-infection with malaria, it shows the severity of clinical manifestations due to increased inflammatory response. Tobe assumed that the host's immune response to worms will have a more severe clinical impact in the Covid-19 case. Keywords: Covid-19, coinfection, malaria, intestinal worms, parasitic diseases

scholarly journals HELICOBACTER PYLORI INFECTION AND IMMUNE PROFILE OF PATIENTS WITH DIFFERENT GASTRODUODENAL DISEASES

2018 ◽  
Vol 55 (2) ◽  
pp. 122-127 ◽  
Author(s):  
Ruth Maria Dias Ferreira VINAGRE ◽  
Igor Dias Ferreira VINAGRE ◽  
Adenielson VILAR-e-SILVA ◽  
Amanda Alves FECURY ◽  
Luisa Caricio MARTINS
Keyword(s):  
Gastric Cancer ◽  
Immune Response ◽  
Helicobacter Pylori ◽  
Gastric Ulcer ◽  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Gastric Biopsies ◽  
Ifn Γ ◽  
H Pylori ◽  
A Prospective Study

ABSTRACT BACKGROUND: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. OBJECTIVE: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. METHODS: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. RESULTS: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. CONCLUSION: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.

Prasugrel inhibits platelet-leukocyte interaction and reduces inflammatory markers in a model of endotoxic shock in the mouse

2012 ◽  
Vol 107 (06) ◽  
pp. 1130-1140 ◽  
Author(s):  
Licia Totani ◽  
Giuseppe Dell’Elba ◽  
Nicola Martelli ◽  
Angelomaria Di Santo ◽  
Antonio Piccoli ◽  
...  
Keyword(s):  
Whole Blood ◽  
Inflammatory Markers ◽  
Active Metabolite ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Endotoxic Shock ◽  
Clinical Manifestations ◽  
Inhibitory Effect ◽  
Agonist Peptide

SummaryPrasugrel, through its active metabolite, reduces atherothrombosis and its clinical manifestations by inhibiting platelet activation and aggregation. Platelets also contribute to inflammation through interaction with different classes of leukocytes. We investigated whether the inhibitory effect of prasugrel on platelets also counteract inflammatory responses. The effect of prasugrel active metabolite, R-138727, was investigated on platelet P-selectin expression, platelet adhesion to polymorphonuclear leukocytes (PMN) and monocytes (MN) and Mac-1 expression in PMN and MN, in vitro, in human cells. The ex vivo effect of prasugrel administration on P-selectin, thromboxane (TXB)2 formation, platelet-PMN conjugates and Mac-1 expression in PMN triggered by PAR-4 agonist peptide was examined in whole blood from healthy mice as well as from mice in which an acute inflammatory reaction was induced by treatment with endotoxin. The effect of prasugrel on inflammatory markers in endotoxin-treated animals was also tested in vivo. R-138727 inhibited agonist-stimulated expression of platelet P-selectin, platelet-PMN and platelet-MN adhesion and platelet-dependent Mac-1 expression in leukocytes. Addition of aspirin did not modify the inhibitory effect elicited by R-138727. Treatment of mice with prasugrel resulted in a profound inhibition of platelet P-selectin expression, TXB2 production, platelet-PMN adhesion and Mac-1 expression in PMN induced by ex vivo stimulation with PAR-4 agonist peptide of whole blood from healthy or endotoxin-treated mice. Measurement of markers revealed that prasugrel reduced TXB2 and tumour necrosis factor-α synthesis and increased nitric oxide metabolites in endotoxin-treated mice in vivo. In conclusion, prasugrel reduces platelet interactions with PMN and MN. Through these effects prasugrel may curb platelet-mediated inflammatory responses.

Changes in corneocyte element concentrations occur in skin inner stratum corneum

1990 ◽  
Vol 48 (2) ◽  
pp. 146-147
Author(s):  
R. R. Warner
Keyword(s):  
Stratum Corneum ◽  
Human Skin ◽  
Element Concentration ◽  
Skin Barrier ◽  
Barrier Properties ◽  
Brick Wall ◽  
Inorganic Elements ◽  
Dry Skin ◽  
Skin Biopsies ◽  
Intercellular Lipid

Keratinocytes undergo maturation during their transit through the viable layers of skin, and then abruptly transform into flattened, anuclear corneocytes that constitute the cellular component of the skin barrier, the stratum corneum (SC). The SC is generally considered to be homogeneous in its structure and barrier properties, and is often shown schematically as a featureless brick wall, the “bricks” being the corneocytes, the “mortar” being intercellular lipid. Previously we showed the outer SC was not homogeneous in its composition, but contained steep gradients of the physiological inorganic elements Na, K and Cl, likely originating from sweat salts. Here we show the innermost corneocytes in human skin are also heterogeneous in composition, undergoing systematic changes in intracellular element concentration during transit into the interior of the SC.Human skin biopsies were taken from the lower leg of individuals with both “good” and “dry” skin and plunge-frozen in a stirred, cooled isopentane/propane mixture.

Alergia à Proteína do Leite de Vaca Persistente em Adulto: Relato de Caso / Persistent Cow’s Milk Allergy in Adult: Case Report

1970 ◽  
Vol 5 (4) ◽  
pp. 51-60
Author(s):  
José Henrique Pereira Pinto ◽  
Renan Lemos de Toledo ◽  
William do Prado Franquelo
Keyword(s):  
Immune Response ◽  
Case Report ◽  
Inflammatory Disease ◽  
Clinical Manifestations ◽  
Milk Proteins ◽  
Cow’S Milk ◽  
Cow's Milk ◽  
Current Prevalence ◽  
Keywords Allergy ◽  
Ige Mediated

RESUMOIntrodução: Alergia à Proteína do Leite de Vaca (APLV) é uma doença inflamatória secundária à reação imunológica contra uma ou mais proteínas do leite de vaca (LV) que afeta principalmente a faixa pediátrica. A real prevalência é discutida em muitos estudos. As manifestações clínicas dependem do tipo da resposta imunológica, ser IgE mediada ou não. Os sintomas se iniciam por volta dos 06 meses de vida e na maioria dos casos, esse processo alérgico regride, com o paciente desenvolvendo tolerância até a adolescência. Casuística: Relata-se um caso de um paciente do sexo masculino, apresentando desde os 6 meses de idade de anafilaxia e broncoespasmo. Nesta época foi levado em hospitais e ambulatórios sendo diagnosticado e tratado como asma apenas, porém sem sucesso. Aos 18 anos, em consulta com especialista foi diagnosticado com APLV, apesar da dieta de exclusão, apresentou diversas reações anafiláticas, devido a ingestão acidental do alérgeno. Discussão: O paciente iniciou os primeiros sintomas quando houve contato com LV e apresentou teste laboratorial com valores compatíveis a patologia. Segundo a literatura a prevalência de APLV cai para menos de 1% aos 6 anos de vida e está persistência pode estar associada a múltiplos fatores, no caso relatado, o paciente não apresentou tolerância até o presente momento. Conclusão: APLV é uma doença usualmente de criança em que, se estas não adquirirem tolerância, complicações podem perdurar indefinidamente. O Diagnóstico precoce e o manejo adequado desta condição, revela grande importância na qualidade de vida e na prevenção de anafilaxia.Palavras chave: Alergia, Proteína do leite de vaca, Anafilaxia. ABSTRACT Introduction: Allergy to cow's milk (CMPA) is an inflammatory disease Introduction: Allergy to cow's milk (CMPA) is an inflammatory disease secondary to immune response against one or more cow's milk proteins (LV) which primarily affects pediatric patients. The current prevalence is discussed in many studies. The clinical manifestations depend on the type of immune response, being IgE mediated or not. Symptoms start at about 06 months of life and in most cases, the allergic process subsides, and the patient develops tolerance through adolescence. Case Report: We report the case of a male patient, who was presenting, since his 06 months of age, anaphylaxis and bronchospasm. At that time he was taken into hospitals and clinics being diagnosed and treated as asthma, but without success. At 18, in consultation with expert was diagnosed with CMPA, and despite the exclusion diet, presented several anaphylactic reactions due to accidental ingestion of the allergen. Discussion: The patient began the first symptoms when there was contact with LV and presented laboratory test values compatible with the pathology. According to the literature the prevalence of CMPA drops to less than 1% to 6 years of life and this persistence can be associated with multiple factors, in our case, the patient did not develop tolerance to date. Conclusion: CMPA is usually a child disease but ,if they do not acquire tolerance, complications can last indefinitely. Early diagnosis and appropriate management of this condition, reveals a great deal on quality of life and prevention of anaphylaxis. Keywords: Allergy, Cow’s milk protein, Anaphylaxis. 

Scabies: A Neglected Global Disease

2020 ◽  
Vol 16 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Alexander K.C. Leung ◽  
Joseph M. Lam ◽  
Kin F. Leong
Keyword(s):  
English Language ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Sarcoptes Scabiei ◽  
Clinical Findings ◽  
Effective Control ◽  
Search Term ◽  
Skin Contact ◽  
Intense Pruritus ◽  
Meta Analyses

Background: Scabies is a skin disease caused by an obligate human parasite mite Sarcoptes scabiei var. hominis. Children under the age of two and elderly individuals are at the greatest risk. Knowledge of this condition is important for an early diagnosis to be made and treatment to be initiated. Objective: The review aimed to familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of scabies. Methods: A search was conducted using Pubmed with the built-in "Clinical Queries" tool. The search term "Scabies" was used. The categories of "epidemiology", "diagnosis", "therapy", "prevention" and "prognosis" had a limited scope for primary clinical studies. Meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews were included. Only papers published in the English language were included. A descriptive, narrative synthesis was provided of the retrieved articles. Results: Worldwide, scabies affects 200 to 300 million individuals annually. The average prevalence is estimated to be 5 to 10% in children of developing countries. Transmission usually occurs after close prolonged skin-to-skin contact. Classic scabies is characterized by an erythematous papular eruption, serpiginous burrows, and intense pruritus. Sites of predilection include the webs of the fingers, volar wrists, lateral aspects of fingers, extensor surfaces of elbows and knees, waist, navel, abdomen, buttocks, groins, and, genitals. A clinical diagnosis of classic scabies can be made on the basis of the history and clinical findings. Other clinical variants include crusted scabies, nodular scabies, and bullous scabies. Finding the mite, ova, or fecal pellets on microscopic examination of scrapings taken from skin lesions confirms the diagnosis of scabies infestation. For eradication of scabies mites, the drugs of choice are topical permethrin and oral ivermectin. Conclusion: Scabies is a highly contagious parasitic cutaneous disease that is stigmatising and debilitating. Increased awareness, accurate diagnosis, and prompt treatment are essential for the effective control of scabies and for the prevention of the spread of the disease.

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