scholarly journals Virulence of Trypanosoma cruzi Strains Is Related to the Differential Expression of Innate Immune Receptors in the Heart

Author(s):  
Tamyres Bernadete Dantas Queiroga ◽  
Nathalie de Sena Pereira ◽  
Denis Dantas da Silva ◽  
Cléber de Mesquita Andrade ◽  
Raimundo Fernandes de Araújo Júnior ◽  
...  

Resistance or susceptibility to T. cruzi infection is dependent on the host immunological profile. Innate immune receptors, such as Toll-like receptors (TLRs/TLR2, TLR4, TLR7, and TLR9) and Nod-like receptors (NLRs/NOD1 and NLRP3 inflammasome) are involved with the resistance against acute experimental T. cruzi infection. Here, we evaluated the impact of T. cruzi virulence on the expression of innate immune receptors and its products in mice. For that, we used six T. cruzi strains/isolates that showed low (AM64/TcIV and 3253/Tc-V), medium (PL1.10.14/TcIII and CL/TcVI), or high (Colombian/Tc-I and Y/TcII) virulence and pathogenicity to the vertebrate host and belonging to the six discrete typing units (DTUs)—TcI to TcVI. Parasitemia, mortality, and myocarditis were evaluated and correlated to the expression of TLRs, NLRs, adapter molecules, cytokines, and iNOS in myocardium by real time PCR. Cytokines (IL-1β, IL-12, TNF-α, and IFN-γ) were quantified in sera 15 days after infection. Our data indicate that high virulent strains of T. cruzi, which generate high parasitemia, severe myocarditis, and 100% mortality in infected mice, inhibit the expression of TLR2, TLR4, TLR9, TRIF, and Myd88 transcripts, leading to a low IL-12 production, when compared to medium and low virulent T. cruzi strains. On the other hand, the high virulent T. cruzi strains induce the upregulation of NLRP3, caspase-1, IL-1β, TNF-α, and iNOS mRNA in heart muscle, compared to low and medium virulent strains, which may contribute to myocarditis and death. Moreover, high virulent strains induce higher levels of IL-1β and TNF-α in sera compared to less virulent parasites. Altogether the data indicate that differential TLR and NLR expression in heart muscle is correlated with virulence and pathogenicity of T cruzi strains. A better knowledge of the immunological mechanisms involved in resistance to T. cruzi infection is important to understand the natural history of Chagas disease, can lead to identification of immunological markers and/or to serve as a basis for alternative therapies.

2013 ◽  
Vol 26 (1) ◽  
pp. 59-73 ◽  
Author(s):  
R. Madonna ◽  
H. Wu ◽  
H. Shelat ◽  
Y-J. Geng

In patients with obesity and diabetes mellitus, abnormal production of inflammatory factors may result in cardiovascular dysfunction. In the current study, we tested the impact of CD1d-mediated innate immune responses on the expression and activation of NFκB in the hearts of adipose diabetic ( db/db) mice. Splenocytes from adult db/db and CD1d-knockout mice of both genders and their wild-type, C57BL/6 and Balb/C counterparts were examined for tumor necrosis factor (TNF)-α and TNF-α receptor type 1. The percentage of natural killer T (NKT) cells in CD3+ T cells was compared with that in nondiabetic control mice. Despite the absence of inflammatory infiltrates, the hearts of db/db mice showed alterations in TNF-α receptor-1 and NFκB activity, including increased expression of both the NFκB p52 and p65 subunits. In the hearts of CD1d-knockout mice, p52 expression was reduced, while p65 expression remained largely unchanged. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was significantly decreased in db/db mice after they swam for 30 minutes. These results provide evidence for CD1d-mediated NFκB activation and diastolic dysfunction in the hearts of db/db mice. Therefore, CD1d-associated abnormalities of innate immune responses and TNF-α production in splenic tissue may contribute to NFκB activation and cardiac dysfunction in type 2 diabetes.


2015 ◽  
Vol 4 (1) ◽  
pp. 1 ◽  
Author(s):  
Jean Fall ◽  
Mahmoud Tanekhy

<p>Garlic is known to possess a vast variety of biological functions. It was reported to be ana a antimicrobial, antithrombotic, anticacer, antioxidant and could improve the immune-system as well as had the capacity to lower serum lipid and glucose levels. The impact of allicin on signaling pathways still needs to be investigated and reports about its effect on cytokine production are inconsistent. In the present study, we investigated the influence of allicin on several carp genes and checked the immediate response of these genes. Direct p-regulation of pro-inflammatory cytokines as IL-1β, TNF-α, IL-10, TLR3, and INF-α, INFγ1 was observed after stimulation of carp head kidney (HK) cells with allicin extract. These results strongly indicate that allicin is responsible for the anti-inflammatory effects. Further, the results suggest that there are potential therapeutic effects of allicin on chronic inflammatory diseases. These effects need more investigations in aquaculture industries.</p>


Author(s):  
Wei-Chun Chou ◽  
Elena Rampanelli ◽  
Xin Li ◽  
Jenny P.-Y. Ting

AbstractImmunometabolism, which is the metabolic reprogramming of anaerobic glycolysis, oxidative phosphorylation, and metabolite synthesis upon immune cell activation, has gained importance as a regulator of the homeostasis, activation, proliferation, and differentiation of innate and adaptive immune cell subsets that function as key factors in immunity. Metabolic changes in epithelial and other stromal cells in response to different stimulatory signals are also crucial in infection, inflammation, cancer, autoimmune diseases, and metabolic disorders. The crosstalk between the PI3K–AKT–mTOR and LKB1–AMPK signaling pathways is critical for modulating both immune and nonimmune cell metabolism. The bidirectional interaction between immune cells and metabolism is a topic of intense study. Toll-like receptors (TLRs), cytokine receptors, and T and B cell receptors have been shown to activate multiple downstream metabolic pathways. However, how intracellular innate immune sensors/receptors intersect with metabolic pathways is less well understood. The goal of this review is to examine the link between immunometabolism and the functions of several intracellular innate immune sensors or receptors, such as nucleotide-binding and leucine-rich repeat-containing receptors (NLRs, or NOD-like receptors), absent in melanoma 2 (AIM2)-like receptors (ALRs), and the cyclic dinucleotide receptor stimulator of interferon genes (STING). We will focus on recent advances and describe the impact of these intracellular innate immune receptors on multiple metabolic pathways. Whenever appropriate, this review will provide a brief contextual connection to pathogenic infections, autoimmune diseases, cancers, metabolic disorders, and/or inflammatory bowel diseases.


Crisis ◽  
2016 ◽  
Vol 37 (4) ◽  
pp. 265-270 ◽  
Author(s):  
Meshan Lehmann ◽  
Matthew R. Hilimire ◽  
Lawrence H. Yang ◽  
Bruce G. Link ◽  
Jordan E. DeVylder

Abstract. Background: Self-esteem is a major contributor to risk for repeated suicide attempts. Prior research has shown that awareness of stigma is associated with reduced self-esteem among people with mental illness. No prior studies have examined the association between self-esteem and stereotype awareness among individuals with past suicide attempts. Aims: To understand the relationship between stereotype awareness and self-esteem among young adults who have and have not attempted suicide. Method: Computerized surveys were administered to college students (N = 637). Linear regression analyses were used to test associations between self-esteem and stereotype awareness, attempt history, and their interaction. Results: There was a significant stereotype awareness by attempt interaction (β = –.74, p = .006) in the regression analysis. The interaction was explained by a stronger negative association between stereotype awareness and self-esteem among individuals with past suicide attempts (β = –.50, p = .013) compared with those without attempts (β = –.09, p = .037). Conclusion: Stigma is associated with lower self-esteem within this high-functioning sample of young adults with histories of suicide attempts. Alleviating the impact of stigma at the individual (clinical) or community (public health) levels may improve self-esteem among this high-risk population, which could potentially influence subsequent suicide risk.


Author(s):  
C. Claire Thomson

This chapter traces the early history of state-sponsored informational filmmaking in Denmark, emphasising its organisation as a ‘cooperative’ of organisations and government agencies. After an account of the establishment and early development of the agency Dansk Kulturfilm in the 1930s, the chapter considers two of its earliest productions, both process films documenting the manufacture of bricks and meat products. The broader context of documentary in Denmark is fleshed out with an account of the production and reception of Poul Henningsen’s seminal film Danmark (1935), and the international context is accounted for with an overview of the development of state-supported filmmaking in the UK, Italy and Germany. Developments in the funding and output of Dansk Kulturfilm up to World War II are outlined, followed by an account of the impact of the German Occupation of Denmark on domestic informational film. The establishment of the Danish Government Film Committee or Ministeriernes Filmudvalg kick-started aprofessionalisation of state-sponsored filmmaking, and two wartime public information films are briefly analysed as examples of its early output. The chapter concludes with an account of the relations between the Danish Resistance and an emerging generation of documentarists.


Author(s):  
Bryan D. Palmer

This article is part of a special Left History series reflecting upon changing currents and boundaries in the practice of left history, and outlining the challenges historians of the left must face in the current tumultuous political climate. This series extends a conversation first convened in a 2006 special edition of Left History (11.1), which asked the question, “what is left history?” In the updated series, contributors were asked a slightly modified question, “what does it mean to write ‘left’ history?” The article charts the impact of major political developments on the field of left history in the last decade, contending that a rising neoliberal and right-wing climate has constructed an environment inhospitable to the discipline’s survival. To remain relevant, Palmer calls for historians of the left to develop a more “open-ended and inclusive” understanding of the left and to push the boundaries of inclusion for a meaningful historical study of the left. To illustrate, Palmer provides a brief materialist history of liquorice to demonstrate the mutability of left history as a historical approach, rather than a set of traditional political concerns.


2020 ◽  
Vol 5 (3) ◽  
pp. 20-24
Author(s):  
Durdona Karimova ◽  

This article discusses the theoretical and practical foundations of the concept of sociolinguistics and the importance of this field in the study of the impact of society on language. It also describes the views of linguists in this regard, the history of the origin and development of the filed, its connection with other disciplines, and explains in detail the sociolinguistic issues with practical examples.In addition, the terms as macro-sociolinguistics and micro-sociolinguistics and sociolinguistic competence are explained.


Author(s):  
Zulpadli Zulpadli

This paper briefly and through theoretical studies will discuss simply the problems formulated, the impact of globalization on Character education in Indonesia, as well as the paradigm of PKN learning and Character education challenges for the younger generation. It is on the ground by the declining awareness and moral values, as well as to increase the values of the characters seen in the young generations. Civic education in Indonesia has been running throughout the history of Indonesian independence, and has gone through various stages and arms, it certainly demands greater hard work of teachers to be able to increase the values of Pancasila and love of the homeland, and practice the character values which is based on the noble values of Indonesian culture into Indonesian youth.


2019 ◽  
Author(s):  
Daryl Brian O'Connor

Suicide is a global health issue accounting for at least 800,000 deaths per annum. Numerous models have been proposed that differ in their emphasis on the role of psychological, social, psychiatric and neurobiological factors in explaining suicide risk. Central to many models is a stress-diathesis component which states that suicidal behavior is the result of an interaction between acutely stressful events and a susceptibility to suicidal behavior (a diathesis). This article presents an overview of studies that demonstrate that stress and dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, are important additional risk factors for suicide. Evidence for other putative stress-related suicide risk factors including childhood trauma, impaired executive function, impulsivity and disrupted sleep are considered together with the impact of family history of suicide, perinatal and epigenetic influences on suicide risk.


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