scholarly journals Role of Cytokines in Experimental and Human Visceral Leishmaniasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Mukesh Samant ◽  
Utkarsha Sahu ◽  
Satish Chandra Pandey ◽  
Prashant Khare
Keyword(s):  
Immune Response ◽  
Animal Models ◽  
Visceral Leishmaniasis ◽  
Disease Progression ◽  
Therapeutic Interventions ◽  
Diagnostic Tools ◽  
Host Protection ◽  
Comprehensive Knowledge ◽  
Prophylactic Measures

Visceral Leishmaniasis (VL) is the most fatal form of disease leishmaniasis. To date, there are no effective prophylactic measures and therapeutics available against VL. Recently, new immunotherapy-based approaches have been established for the management of VL. Cytokines, which are predominantly produced by helper T cells (Th) and macrophages, have received great attention that could be an effective immunotherapeutic approach for the treatment of human VL. Cytokines play a key role in forming the host immune response and in managing the formation of protective and non-protective immunities during infection. Furthermore, immune response mediated through different cytokines varies from different host or animal models. Various cytokines viz. IFN-γ, IL-2, IL-12, and TNF-α play an important role during protection, while some other cytokines viz. IL-10, IL-6, IL-17, TGF-β, and others are associated with disease progression. Therefore, comprehensive knowledge of cytokine response and their interaction with various immune cells is very crucial to determine appropriate immunotherapies for VL. Here, we have discussed the role of cytokines involved in VL disease progression or host protection in different animal models and humans that will determine the clinical outcome of VL and open the path for the development of rapid and accurate diagnostic tools as well as therapeutic interventions against VL.

Inflammation in Complicated Pregnancy and Its Outcome

2016 ◽  
Vol 33 (14) ◽  
pp. 1337-1356 ◽  
Author(s):  
Ram Kalagiri ◽  
Timothy Carder ◽  
Saiara Choudhury ◽  
Niraj Vora ◽  
Amie Ballard ◽  
...  
Keyword(s):  
Preterm Labor ◽  
Maternal Obesity ◽  
Normal Pregnancy ◽  
Adverse Outcomes ◽  
Therapeutic Interventions ◽  
Inflammatory Factors ◽  
Diagnostic Tools ◽  
Inflammatory Reactions ◽  
Mortality And Morbidity

Background Normal pregnancy relies on a careful balance between immune tolerance and suppression. It is known that strict regulation of maternal immune function, in addition to components of inflammation, is paramount to successful pregnancy, and any imbalance between proinflammatory and anti-inflammatory cytokines and chemokines can lead to aberrant inflammation, often seen in complicated pregnancies. Inflammation in complicated pregnancies is directly associated with increased mortality and morbidity of the mother and offspring. Aberrant inflammatory reactions in complicated pregnancies often lead to adverse outcomes, such as spontaneous abortion, preterm labor, intrauterine growth restriction, and fetal demise. The role of inflammation in different stages of normal pregnancy is reviewed, compared, and contrasted with aberrant inflammation in complicated pregnancies. The complications addressed are preterm labor, pregnancy loss, infection, preeclampsia, maternal obesity, gestational diabetes mellitus, autoimmune diseases, and inflammatory bowel disease. Aim This article examines the role of various inflammatory factors contributing to aberrant inflammation in complicated pregnancies. By understanding the aberrant inflammatory process in complicated pregnancies, novel diagnostic tools and therapeutic interventions for modulating it appropriately can be identified.

scholarly journals Immunogenetics of leishmanial and mycobacterial infections: the Belem Family Study

1997 ◽  
Vol 352 (1359) ◽  
pp. 1331-1345 ◽  
Author(s):  
J. M. Blackwell ◽  
G. F. Black ◽  
C. S. Peacock ◽  
E. N. Miller ◽  
D. Sibthorpe ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Candidate Gene ◽  
Mouse Chromosome ◽  
Human Disease ◽  
Disease Susceptibility ◽  
Allelic Association ◽  
Chromosome 11 ◽  
Mycobacterial Infections

In the 1970s and 1980s, analysis of recombinant inbred, congenic and recombinant haplotype mouse strains permitted us to effectively ‘scan’ the murine genome for genes controlling resistance and susceptibility to leishmanial infections. Five major regions of the genome were implicated in the control of infections caused by different Leishmania species which, because they show conserved synteny with regions of the human genome, immediately provides candidate gene regions for human disease susceptibility genes. A common intramacrophage niche for leishmanial and mycobacterial pathogens, and a similar spectrum of immune response and disease phenotypes, also led to the prediction that the same genes/candidate gene regions might be responsible for genetic susceptibility to mycobacterial infections such as leprosy and tuberculosis. Indeed, one of the murine genes ( Nramp1 ) was identified for its role in controlling a range of intramacrophage pathogens including leishmania, salmonella and mycobacterium infections. In recent studies, multicase family data on visceral leishmaniasis and the mycobacterial diseases, tuberculosis and leprosy, have been collected from north–eastern Brazil and analysed to determine the role of these candidate genes/regions in determining disease susceptibility. Complex segregation analysis provides evidence for one or two major genes controlling susceptibility to tuberculosis in this population. Family–based linkage analyses (combined segregation and linkage analysis; sib–pair analysis), which have the power to detect linkage between marker loci in candidate gene regions and the putative disease susceptibility genes over 10–;20 centimorgans, and transmission disequilibrium testing, which detects allelic associations over 1 centimorgan ( ca. 1 megabase), have been used to examine the role of four regions in determining disease susceptibility and/or immune response phenotype. Our results demonstrate: (i) the major histocompatibility complex (MHC: H–2 in mouse, HLA in man: mouse chromosome 17/human 6p; candidates class II and class III including TNFalpha/beta genes) shows both linkage to, and allelic association with, leprosy per se , but is only weakly associated with visceral leishmaniasis and shows neither linkage to nor allelic association with tuberculosis; (ii) no evidence for linkage between NRAMP1 , the positionally cloned candidate for the murine macrophage resistance gene Ity/Lsh/Bcg (mouse chromosome 1/human 2q35), and susceptibility to tuberculosis or visceral leishmaniasis could be demonstrated in this Brazilian population; (iii) the region of human chromosome 17q (candidates NOS2A , SCYA2–5 ) homologous with distal mouse chromosome 11, originally identified as carrying the Scl1 gene controlling healing versus nonhealing responses to Leishmania major , is linked to tuberculosis susceptibility; and (iv) the ‘T helper 2’ cytokine gene cluster (proximal murine chromosome 11/human 5q; candidates IL4, IL5, IL9, IRF1, CD14) controlling later phases of murine L. major infection, is not linked to human disease susceptibility for any of the three infections, but shows linkage to and highly significant allelic association with ability to mount an immune response to mycobacterial antigens. These studies demonstrate that the ‘mouse–to–man’ strategy, refined by our knowledge of the human immune response to infection, can lead to the identification of important candidate gene regions in man.

The role of cytokines in immunological tolerance: potential for therapy

2000 ◽  
Vol 2 (9) ◽  
pp. 1-20 ◽  
Author(s):  
Mark Harber ◽  
Anette Sundstedt ◽  
David Wraith
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Animal Models ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immunological Tolerance ◽  
Immunomodulatory Effects ◽  
Clinical Potential

Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

scholarly journals Memory T Cells in Flavivirus Vaccination

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 73 ◽  
Author(s):  
Guangyu Li ◽  
Cody Teleki ◽  
Tian Wang
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Animal Models ◽  
Yellow Fever ◽  
Protective Immunity ◽  
Memory T Cells ◽  
Host Protection ◽  
Tick Borne Encephalitis ◽  
Flavivirus Infection

Flaviviruses include many medically important viruses, such as Dengue virus (DENV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), West Nile (WNV), yellow fever (YFV), and Zika viruses (ZIKV). Currently, there are licensed human vaccines for DENV, JEV, TBEV and YFV, but not for WNV or ZIKV. Memory T cells play a central role in adaptive immunity and are important for host protection during flavivirus infection. In this review, we discuss recent findings from animal models and clinical trials and provide new insights into the role of memory T cells in host protective immunity upon vaccination with the licensed flavivirus vaccines.

scholarly journals Etiology and Risk Factors of Febrile Seizure – An Update

2012 ◽  
Vol 34 (3) ◽  
pp. 103-112 ◽  
Author(s):  
Gopen Kumar Kundu ◽  
F Rabin ◽  
ER Nandi ◽  
Naveen Sheikh ◽  
Shaheen Akhter
Keyword(s):  
Risk Factors ◽  
World Literature ◽  
Viral Infections ◽  
Febrile Seizures ◽  
Causative Factor ◽  
Etiologic Agent ◽  
Therapeutic Interventions ◽  
Diagnostic Tools ◽  
Familial Predisposition

Febrile seizures (FS) are the most common convulsive event in children. This condition has been described since the time of Hippocrates. The etiology of the febrile seizures are still unclear. In FS, there is a strong familial predisposition. This does not exclude infections as a causative factor because subtle genetic polymorphisms have been demonstrated to affect the course of infections. In an earlier review of the world literature (1924-1964), except for roseola infantum, viral infections as a cause of febrile seizures were rarely diagnosed. Reports of viral infections in the etiology of febrile seizures have increased in number in the past decade. In the first half of the twentieth century, infections identified with febrile seizures were mainly upper respiratory in type and the etiologic agent was unknown or bacterial. We review i) the role of infection – viral and bacterial; ii) the role of genetic and environmental factors; iii) the role of electrolyte and metabolic factors; and iv) the role of cytokines. With the help of new diagnostic tools such as PCR, the viral agents are detected in CSF far more often than previously thought, even in the absence of pleocytosis of the CSF. This makes it difficult to distinguish FS from acute encephalitis. FS may be caused by neuroinvasion or intracerebral activation of viruses. By reviewing etiology and risk factors of FS we can identify the points to be focused in therapeutic interventions and trials and also the fields of future studies will be explored. DOI: http://dx.doi.org/10.3329/bjch.v34i3.10361 BJCH 2010; 34(3): 103-112

scholarly journals The Role of microRNAs and Long Non-Coding RNAs in the Regulation of the Immune Response to Mycobacterium tuberculosis Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Manikuntala Kundu ◽  
Joyoti Basu
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Signaling Pathways ◽  
Defense Mechanisms ◽  
Latent Tuberculosis ◽  
Mycobacterial Infection ◽  
Diagnostic Tools ◽  
Mycobacterium Tuberculosis Infection ◽  
Non Coding Rnas

Non-coding RNAs have emerged as critical regulators of the immune response to infection. MicroRNAs (miRNAs) are small non-coding RNAs which regulate host defense mechanisms against viruses, bacteria and fungi. They are involved in the delicate interplay between Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), and its host, which dictates the course of infection. Differential expression of miRNAs upon infection with M. tuberculosis, regulates host signaling pathways linked to inflammation, autophagy, apoptosis and polarization of macrophages. Experimental evidence suggests that virulent M. tuberculosis often utilize host miRNAs to promote pathogenicity by restricting host-mediated antibacterial signaling pathways. At the same time, host- induced miRNAs augment antibacterial processes such as autophagy, to limit bacterial proliferation. Targeting miRNAs is an emerging option for host-directed therapies. Recent studies have explored the role of long non-coding RNA (lncRNAs) in the regulation of the host response to mycobacterial infection. Among other functions, lncRNAs interact with chromatin remodelers to regulate gene expression and also function as miRNA sponges. In this review we attempt to summarize recent literature on how miRNAs and lncRNAs are differentially expressed during the course of M. tuberculosis infection, and how they influence the outcome of infection. We also discuss the potential use of non-coding RNAs as biomarkers of active and latent tuberculosis. Comprehensive understanding of the role of these non-coding RNAs is the first step towards developing RNA-based therapeutics and diagnostic tools for the treatment of TB.

Increasing risk factors of non-alcoholic fatty liver disease, a look into chronic periodontitis and insulin resistance

2022 ◽  
Vol 22 ◽  
Author(s):  
Sreenu Thalla ◽  
Kamaraj R ◽  
Kavitha A
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Immune Response ◽  
Liver Disease ◽  
Fatty Liver ◽  
Disease Progression ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract: Non-alcoholic fatty liver disease (NAFLD) is marked by the excessive intrusion of triglycerides into hepatocytes without any role of alcohol consumption. Various risk factors have been attributed to this disease pathogenesis which involves metabolic disorders, immune response, and even an intricate relationship between the two. The role of insulin resistance (IR) in NAFLD has long been known; however, the molecular basis of disease progression under this metabolic backdrop is still being investigated. Similarly, the periodontitis-mediated immune response is another major factor involved in NAFLD manifestation which has generated huge interest. The prevalence of pathogenic bacteria elicits a strong immune response which according to studies shows a strong correlation with NAFLD state. Such pre-existing conditions have a strong probability of explaining the disease onset. Additionally, increasing reports of inflammatory response and its links to insulin resistance have further increased the scope of understanding NAFLD. Through this review, we aim to elaborate on these factors explaining their role in the disease progression.

scholarly journals The Role of IL-33 in Rheumatic Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Lihua Duan ◽  
Jie Chen ◽  
Feili Gong ◽  
Guixiu Shi
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Disease Progression ◽  
Rheumatic Diseases ◽  
Orphan Receptor ◽  
Expression Levels ◽  
Interleukin 33

Interleukin-33 (IL-33), a novel member of IL-1 family, has been recently implicated in several inflammatory and autoimmune diseases. IL-33 can be produced by various types of tissues and cells and induce gene expression of Th2-associated cytokines via binding to the orphan receptor ST2. By promoting Th2 type immune response, IL-33 plays important roles in the allergy, whereas its function in autoimmune diseases attracts more attention. Recent studies reported the correlation of IL-33 with rheumatic diseases, and most of them found that the IL-33 expression levels were consistent with disease activity and development. Furthermore, evidence has indicated that IL-33-related treatment may ameliorate the pathogenic conditions and attenuate disease progression of those rheumatic diseases. Therefore, elucidation of the roles of IL-33 in rheumatic diseases would be beneficial to understand the pathogenesis and therapy of these diseases. In this paper, we will summarize the roles of IL-33 in the rheumatic diseases.

Effects of aerobic exercise training in animal models of hypertension.

2015 ◽  
Vol 13 ◽  
pp. 307
Author(s):  
Renata Kelly Da Palma ◽  
Christiane Malfitano ◽  
Guilherme Lemos Shimojo ◽  
Iris Callado Sanches ◽  
Kátia De Angelis
Keyword(s):  
Blood Pressure ◽  
Animal Models ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Causes Of Death ◽  
Reduce Blood Pressure ◽  
Aerobic Exercise Training ◽  
Therapeutic Interventions ◽  
Treatment Of Hypertension

Background: Hypertension is one of the leading causes of death due to stroke, heart attack and kidney failure. The understanding of the pathophysiological mechanisms involved in its development and maintenance is critical to potential therapeutic interventions. Thus, animal models of hypertension have been used in the study of this disease for many years. Objective: To investigated the effects of dynamic aerobic exercise training as a non-pharmacological approach for the management of hypertension in animal models. Method/Design: This study is a literature review conducted in the Medline database. Results: The results demonstrated that aerobic exercise training may reduce blood pressure in different rat models of hypertension. Conclusions: The dynamic aerobic exercise can reduced blood pressure in different animal models of hypertension by mechanisms that involving neurohumoral changes, reinforcing the important role of this approach in the treatment of hypertension and its associated disorders

scholarly journals Immune correlates of tuberculosis disease and risk translate across species

2020 ◽  
Vol 12 (528) ◽  
pp. eaay0233 ◽  
Author(s):  
Mushtaq Ahmed ◽  
Shyamala Thirunavukkarasu ◽  
Bruce A. Rosa ◽  
Kimberly A. Thomas ◽  
Shibali Das ◽  
...  
Keyword(s):  
Animal Models ◽  
Disease Progression ◽  
Inbred Mouse ◽  
Gene Signature ◽  
Immune Correlates ◽  
Diversity Outbred ◽  
Outbred Mouse ◽  
Immune Pathways ◽  
Tuberculosis Disease

One quarter of the world’s population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Although most infected individuals successfully control or clear the infection, some individuals will progress to TB disease. Immune correlates identified using animal models are not always effectively translated to human TB, thus resulting in a slow pace of translational discoveries from animal models to human TB for many platforms including vaccines, therapeutics, biomarkers, and diagnostic discovery. Therefore, it is critical to improve our poor understanding of immune correlates of disease and protection that are shared across animal TB models and human TB. In this study, we have provided an in-depth identification of the conserved and diversified gene/immune pathways in TB models of nonhuman primate and diversity outbred mouse and human TB. Our results show that prominent differentially expressed genes/pathways induced during TB disease progression are conserved in genetically diverse mice, macaques, and humans. In addition, using gene-deficient inbred mouse models, we have addressed the functional role of individual genes comprising the gene signature of disease progression seen in humans with Mtb infection. We show that genes representing specific immune pathways can be protective, detrimental, or redundant in controlling Mtb infection and translate into identifying immune pathways that mediate TB immunopathology in humans. Together, our cross-species findings provide insights into modeling TB disease and the immunological basis of TB disease progression.

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