scholarly journals Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis

2019 ◽  
Vol 7 (12) ◽  
pp. 695 ◽  
Author(s):  
Camila dos Santos Meira ◽  
Lashitew Gedamu
Keyword(s):  
Immune Cells ◽  
Rna Virus ◽  
Clinical Manifestations ◽  
Host Immunity ◽  
Host Cells ◽  
Health Concern ◽  
Insect Vector ◽  
Self Healing ◽  
Cutaneous Lesions ◽  
Adaptive Immune Cells

The intracellular protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a vector-borne disease of major public health concern, estimated to affect 12 million people worldwide. The clinical manifestations of leishmaniasis are highly variable and can range from self-healing localized cutaneous lesions to life-threatening disseminated visceral disease. Once introduced into the skin by infected sandflies, Leishmania parasites interact with a variety of immune cells, such as neutrophils, monocytes, dendritic cells (DCs), and macrophages. The resolution of infection requires a finely tuned interplay between innate and adaptive immune cells, culminating with the activation of microbicidal functions and parasite clearance within host cells. However, several factors derived from the host, insect vector, and Leishmania spp., including the presence of a double-stranded RNA virus (LRV), can modulate the host immunity and influence the disease outcome. In this review, we discuss the immune mechanisms underlying the main forms of leishmaniasis, some of the factors involved with the establishment of infection and disease severity, and potential approaches for vaccine and drug development focused on host immunity.

scholarly journals Tuning cancer fate: the unremitting role of host immunity

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170006 ◽  
Author(s):  
B. Calì ◽  
B. Molon ◽  
A. Viola
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tumour Progression ◽  
Host Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Immune Cell Subsets ◽  
Therapeutic Protocols

Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site. This pliable interplay between immune and malignant cells is a relentless process that has been concisely organized in three different phases: elimination, equilibrium and escape. In this review, we aim to depict the distinct immune cell subsets and immune-mediated responses characterizing the tumour landscape throughout the three interconnected phases. Importantly, the identification of key immune players and molecules involved in the dynamic crosstalk between tumour and immune system has been crucial for the introduction of reliable prognostic factors and effective therapeutic protocols against cancers.

scholarly journals Can We Harness Immune Responses to Improve Drug Treatment in Leishmaniasis?

2020 ◽  
Vol 8 (7) ◽  
pp. 1069
Author(s):  
Raphael Taiwo Aruleba ◽  
Katharine C. Carter ◽  
Frank Brombacher ◽  
Ramona Hurdayal
Keyword(s):  
Immune Responses ◽  
Economic Status ◽  
Clinical Manifestations ◽  
Steady Increase ◽  
Clinical Use ◽  
Self Healing ◽  
Cutaneous Lesions ◽  
Vector Borne ◽  
Visceral Disease ◽  
Control And Eradication

Leishmaniasis is a vector-borne parasitic disease that has been neglected in priority for control and eradication of malaria, tuberculosis, and HIV/AIDS. Collectively, over one seventh of the world’s population is at risk of being infected with 0.7–1.2 million new infections reported annually. Clinical manifestations range from self-healing cutaneous lesions to fatal visceral disease. The first anti-leishmanial drugs were introduced in the 1950′s and, despite several shortcomings, remain the mainstay for treatment. Regardless of this and the steady increase in infections over the years, particularly among populations of low economic status, research on leishmaniasis remains under funded. This review looks at the drugs currently in clinical use and how they interact with the host immune response. Employing chemoimmunotherapeutic approaches may be one viable alternative to improve the efficacy of novel/existing drugs and extend their lifespan in clinical use.

scholarly journals Analyses of Leishmania-LRV Co-Phylogenetic Patterns and Evolutionary Variability of Viral Proteins

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2305
Author(s):  
Alexei Y. Kostygov ◽  
Danyil Grybchuk ◽  
Yulia Kleschenko ◽  
Daniil S. Chistyakov ◽  
Alexander N. Lukashev ◽  
...  
Keyword(s):  
Rna Virus ◽  
Clinical Manifestations ◽  
Purifying Selection ◽  
Viral Proteins ◽  
Small Scale ◽  
Self Healing ◽  
Genes Encoding ◽  
Leishmania Spp ◽  
Life Threatening ◽  
Vector Borne

Leishmania spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of Leishmania RNA virus (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate host. The two viral species, LRV1 and LRV2 infect species of the subgenera Viannia and Leishmania, respectively. In this work we investigated co-phylogenetic patterns of leishmaniae and their viruses on a small scale (LRV2 in L. major) and demonstrated their predominant coevolution, occasionally broken by intraspecific host switches. Our analysis of the two viral genes, encoding the capsid and RNA-dependent RNA polymerase (RDRP), revealed them to be under the pressure of purifying selection, which was considerably stronger for the former gene across the whole tree. The selective pressure also differs between the LRV clades and correlates with the frequency of interspecific host switches. In addition, using experimental (capsid) and predicted (RDRP) models we demonstrated that the evolutionary variability across the structure is strikingly different in these two viral proteins.

scholarly journals Adipokine-Modulated Immunological Homeostasis Shapes the Pathophysiology of Inflammatory Bowel Disease

2020 ◽  
Vol 21 (24) ◽  
pp. 9564
Author(s):  
Yi-Wen Tsai ◽  
Shin-Huei Fu ◽  
Jia-Ling Dong ◽  
Ming-Wei Chien ◽  
Yu-Wen Liu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gastrointestinal Tract ◽  
Immune Cells ◽  
Bowel Disease ◽  
Health Concern ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Inflammatory Bowel ◽  
Colon Diseases ◽  
Immunological Homeostasis

Inflammatory colon diseases, which are a global health concern, include a variety of gastrointestinal tract disorders, such as inflammatory bowel disease and colon cancer. The pathogenesis of these colon disorders involves immune alterations with the pronounced infiltration of innate and adaptive immune cells into the intestines and the augmented expression of mucosal pro-inflammatory cytokines stimulated by commensal microbiota. Epidemiological studies during the past half century have shown that the proportion of obese people in a population is associated with the incidence and pathogenesis of gastrointestinal tract disorders. The advancement of understanding of the immunological basis of colon disease has shown that adipocyte-derived biologically active substances (adipokines) modulate the role of innate and adaptive immune cells in the progress of intestinal inflammation. The biomedical significance in immunological homeostasis of adipokines, including adiponectin, leptin, apelin and resistin, is clear. In this review, we highlight the existing literature on the effect and contribution of adipokines to the regulation of immunological homeostasis in inflammatory colon diseases and discuss their crucial roles in disease etiology and pathogenesis, as well as the implications of these results for new therapies in these disorders.

scholarly journals Early Leukocyte Responses in Ex-Vivo Models of Healing and Non-Healing Human Leishmania (Viannia) panamensis Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Maria Adelaida Gomez ◽  
Ashton Trey Belew ◽  
Adriana Navas ◽  
Mariana Rosales-Chilama ◽  
Julieth Murillo ◽  
...  
Keyword(s):  
Host Cell ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Current Knowledge ◽  
Human Macrophage ◽  
Type I ◽  
Self Healing ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Early host-pathogen interactions drive the host response and shape the outcome of natural infections caused by intracellular microorganisms. These interactions involve a number of immune and non-immune cells and tissues, along with an assortment of host and pathogen-derived molecules. Our current knowledge has been predominantly derived from research on the relationships between the pathogens and the invaded host cell(s), limiting our understanding of how microbes elicit and modulate immunological responses at the organismal level. In this study, we explored the early host determinants of healing and non-healing responses in human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) panamensis. We performed a comparative transcriptomic profiling of peripheral blood mononuclear cells from healthy donors (PBMCs, n=3) exposed to promastigotes isolated from patients with chronic (CHR, n=3) or self-healing (SH, n=3) CL, and compared these to human macrophage responses. Transcriptomes of L. V. panamensis-infected PBMCs showed enrichment of functional gene categories derived from innate as well as adaptive immune cells signatures, demonstrating that Leishmania modulates adaptive immune cell functions as early as after 24h post interaction with PBMCs from previously unexposed healthy individuals. Among differentially expressed PBMC genes, four broad categories were commonly modulated by SH and CHR strains: cell cycle/proliferation/differentiation, metabolism of macromolecules, immune signaling and vesicle trafficking/transport; the first two were predominantly downregulated, and the latter upregulated in SH and CHR as compared to uninfected samples. Type I IFN signaling genes were uniquely up-regulated in PBMCs infected with CHR strains, while genes involved in the immunological synapse were uniquely downregulated in SH infections. Similarly, pro-inflammatory response genes were upregulated in isolated macrophages infected with CHR strains. Our data demonstrate that early responses during Leishmania infection extend beyond innate cell and/or phagocytic host cell functions, opening new frontiers in our understanding of the triggers and drivers of human CL.

scholarly journals Immune Cells Are Required for Cutaneous Ulceration in a Swine Model of Chancroid

1999 ◽  
Vol 67 (9) ◽  
pp. 4963-4967 ◽  
Author(s):  
Lani R. San Mateo ◽  
Kristen L. Toffer ◽  
Paul E. Orndorff ◽  
Thomas H. Kawula
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Human Infection ◽  
Host Cells ◽  
Swine Model ◽  
Ulcer Formation ◽  
Cutaneous Lesions ◽  
Ulcer Disease ◽  
Sexually Transmitted ◽  
Bacterial Agent

ABSTRACT Cutaneous lesions of the human sexually transmitted genital ulcer disease chancroid are characterized by the presence of intraepidermal pustules, keratinocyte cytopathology, and epidermal and dermal erosion. These lesions are replete with neutrophils, macrophages, and CD4+ T cells and contain very low numbers of cells ofHaemophilus ducreyi, the bacterial agent of chancroid. We examined lesion formation by H. ducreyi in a pig model by using cyclophosphamide (CPA)-induced immune cell deficiency to distinguish between host and bacterial contributions to chancroid ulcer formation. Histologic presentation of H. ducreyi-induced lesions in CPA-treated pigs differed from ulcers that developed in immune-competent animals in that pustules did not form and surface epithelia remained intact. However, these lesions had significant suprabasal keratinocyte cytotoxicity. These results demonstrate that the host immune response was required for chancroid ulceration, while bacterial products were at least partially responsible for the keratinocyte cytopathology associated with chancroid lesions in the pig. The low numbers of H. ducreyi present in lesions in humans and immune-competent pigs have prevented localization of these organisms within skin. However, H. ducreyi organisms were readily visualized in lesion biopsies from infected CPA-treated pigs by immunoelectron microscopy. These bacteria were extracellular and associated with necrotic host cells in the epidermis and dermis. The relative abundance of H. ducreyi in inoculated CPA-treated pig skin suggests control of bacterial replication by host immune cells during natural human infection.

scholarly journals Inhibition of MALT1 Decreases Neuroinflammation and Pathogenicity of Virulent Rabies Virus in Mice

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
E. Kip ◽  
J. Staal ◽  
H. G. Tima ◽  
L. Verstrepen ◽  
M. Romano ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Virus Strain ◽  
Immune Cells ◽  
Rna Virus ◽  
Brain Inflammation ◽  
Disease Development ◽  
Adaptive Immune Cells ◽  
Rabies Virus Strain ◽  
The Impact

ABSTRACTRabies virus is a neurovirulent RNA virus, which causes about 59,000 human deaths each year. Treatment for rabies does not exist due to incomplete understanding of the pathogenesis. MALT1 mediates activation of several immune cell types and is involved in the proliferation and survival of cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, leading to the expression of immunoregulatory genes. Here, we examined the impact of genetic or pharmacological MALT1 inhibition in mice on disease development after infection with the virulent rabies virus strain CVS-11. Morbidity and mortality were significantly delayed inMalt1−/−compared toMalt1+/+mice, and this effect was associated with lower viral load, proinflammatory gene expression, and infiltration and activation of immune cells in the brain. Specific deletion ofMalt1in T cells also delayed disease development, while deletion in myeloid cells, neuronal cells, or NK cells had no effect. Disease development was also delayed in mice treated with the MALT1 protease inhibitor mepazine and in knock-in mice expressing a catalytically inactive MALT1 mutant protein, showing an important role of MALT1 proteolytic activity. The described protective effect of MALT1 inhibition against infection with a virulent rabies virus is the precise opposite of the sensitizing effect of MALT1 inhibition that we previously observed in the case of infection with an attenuated rabies virus strain. Together, these data demonstrate that the role of immunoregulatory responses in rabies pathogenicity is dependent on virus virulence and reveal the potential of MALT1 inhibition for therapeutic intervention.IMPORTANCERabies virus is a neurotropic RNA virus that causes encephalitis and still poses an enormous challenge to animal and public health. Efforts to establish reliable therapeutic strategies have been unsuccessful and are hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protease that mediates the activation of several innate and adaptive immune cells in response to multiple receptors, and therapeutic MALT1 targeting is believed to be a valid approach for autoimmunity and MALT1-addicted cancers. Here, we study the impact of MALT1 deficiency on brain inflammation and disease development in response to infection of mice with the highly virulent CVS-11 rabies virus. We demonstrate that pharmacological or genetic MALT1 inhibition decreases neuroinflammation and extends the survival of CVS-11-infected mice, providing new insights in the biology of MALT1 and rabies virus infection.

scholarly journals Mumps Orchitis: Clinical Aspects and Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Han Wu ◽  
Fei Wang ◽  
Dongdong Tang ◽  
Daishu Han
Keyword(s):  
Male Fertility ◽  
Inflammatory Responses ◽  
Rna Virus ◽  
Host Cells ◽  
High Rate ◽  
Health Concern ◽  
Clinical Aspects ◽  
Adult Men ◽  
Testicular Cells ◽  
Negative Sense

The causative agent of mumps is a single-stranded, non-segmented, negative sense RNA virus belonging to the Paramyxoviridae family. Besides the classic symptom of painfully swollen parotid salivary glands (parotitis) in mumps virus (MuV)-infected men, orchitis is the most common form of extra-salivary gland inflammation. Mumps orchitis frequently occurs in young adult men, and leads to pain and swelling of the testis. The administration of MuV vaccines in children has been proven highly effective in reducing the incidence of mumps. However, a recent global outbreak of mumps and the high rate of orchitis have recently been considered as threats to male fertility. The pathogenesis of mumps orchitis remains largely unclear due to lack of systematic clinical data analysis and animal models studies. The alarming increase in the incidence of mumps orchitis and the high risk of the male fertility have thus become a major health concern. Recent studies have revealed the mechanisms by which MuV-host cells interact and MuV infection induces inflammatory responses in testicular cells. In this mini-review, we highlight advances in our knowledge of the clinical aspects and possible mechanisms of mumps orchitis.

scholarly journals Immunobiotics mechanisms of action and prospects of use in veterinary medicine

2020 ◽  
Vol 210 ◽  
pp. 06017
Author(s):  
Aleksandr Refeld ◽  
Anna Bogdanova ◽  
Evgeniya Prazdnova ◽  
Alexey Beskopylny ◽  
Anastasiya Olshevskaya ◽  
...  
Keyword(s):  
Veterinary Medicine ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Host Immunity ◽  
Complex Action ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Increasing Trend ◽  
Cellular Components

Probiotics are becoming more and more common means of combating intestinal diseases of various origins: infectious pathologies, chronic inflammation, autoimmune disorders. The complex action, coupled with low side effects, makes probiotics promising drugs, especially in veterinary medicine, with an increasing trend towards the inefficient use of antibiotics in the livestock industry. One of the main mechanisms of probiotics action - modulation of host immunity - is perhaps the most difficult and, at the same time, the most actively studied since it is crucial for therapy. Immunobiotics (probiotics that modulate the host's immune response) interact with various innate and adaptive immune cells, changing the expression of pro- and anti-inflammatory cytokines. This action is provided by both the cellular components of probiotic microorganisms and their metabolites and is primarily associated with the host's immunocompetent cells' pattern-recognition receptors, although other molecular mechanisms also exist. This review aims to briefly describe both the molecular mechanisms of immunomodulation by probiotics and the prospects for their use in veterinary medicine.

scholarly journals Thermoresponsive Copolymer Nanovectors Improve the Bioavailability of Retrograde Inhibitors in the Treatment of Leishmania Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Evan Craig ◽  
Anna Calarco ◽  
Raffaele Conte ◽  
Veronica Ambrogi ◽  
Giovanna Gomez d’Ayala ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Mass Spectrometry Analysis ◽  
Self Healing ◽  
Cutaneous Lesions ◽  
Spectrometry Analysis ◽  
Nanoparticle Aggregates ◽  
Hydrophobic Molecule ◽  
Infected Cells ◽  
Viable Approach ◽  
Drug Resistant Strains

Clinical manifestations of leishmaniasis range from self-healing, cutaneous lesions to fatal infections of the viscera. With no preventative Leishmania vaccine available, the frontline option against leishmaniasis is chemotherapy. Unfortunately, currently available anti-Leishmania drugs face several obstacles, including toxicity that limits dosing and emergent drug resistant strains in endemic regions. It is, therefore, imperative that more effective drug formulations with decreased toxicity profiles are developed. Previous studies had shown that 2-(((5-Methyl-2-thienyl)methylene)amino)-N-phenylbenzamide (also called Retro-2) has efficacy against Leishmania infections. Structure–activity relationship (SAR) analogs of Retro-2, using the dihydroquinazolinone (DHQZ) base structure, were subsequently described that are more efficacious than Retro-2. However, considering the hydrophobic nature of these compounds that limits their solubility and uptake, the current studies were initiated to determine whether the solubility of Retro-2 and its SAR analogs could be enhanced through encapsulation in amphiphilic polymer nanoparticles. We evaluated encapsulation of these compounds in the amphiphilic, thermoresponsive oligo(ethylene glycol) methacrylate-co-pentafluorostyrene (PFG30) copolymer that forms nanoparticle aggregates upon heating past temperatures of 30°C. The hydrophobic tracer, coumarin 6, was used to evaluate uptake of a hydrophobic molecule into PFG30 aggregates. Mass spectrometry analysis showed considerably greater delivery of encapsulated DHQZ analogs into infected cells and more rapid shrinkage of L. amazonensis communal vacuoles. Moreover, encapsulation in PFG30 augmented the efficacy of Retro-2 and its SAR analogs to clear both L. amazonensis and L. donovani infections. These studies demonstrate that encapsulation of compounds in PFG30 is a viable approach to dramatically increase bioavailability and efficacy of anti-Leishmania compounds.

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