Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis

Author(s):  
Thalia Pacheco-Fernandez ◽  
Greta Volpedo ◽  
Chaitenya Verma ◽  
Abhay R. Satoskar

Leishmaniasis is a vector-borne Neglected Tropical Disease (NTD) transmitted by the sand fly and is a major public health problem worldwide. Infections caused by Leishmania clinically manifest as a wide range of diseases, such as cutaneous (CL), diffuse cutaneous (DCL), mucosal (MCL) and visceral leishmaniasis (VL). The host innate and adaptative immune responses play critical roles in the defense against leishmaniasis. However, Leishmania parasites also manipulate the host immune response for their survival and replication. In addition, other factors such as sand fly salivary proteins and microbiota also promote disease susceptibility and parasite spread by modulating local immune response. Thus, a complex interplay between parasite, sand fly and the host immunity governs disease severity and outcome. In this review, we discuss the host immune response during Leishmania infection and highlight the factors associated with resistance or susceptibility.

Author(s):  
Elsy Nalleli Loria-Cervera ◽  
Fernando Jose Andrade-Narvaez

Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.


Author(s):  
Laura Sánchez-García ◽  
Armando Perez-Torres ◽  
Samira Muñoz-Cruz ◽  
Jorge Morales-Montor ◽  
Ingeborg Becker

Mast cells (MCs) play a crucial role during infections with Leishmania, that is transmitted through the bite of an infected sand fly that injects saliva together with the parasite. Sand fly saliva is a complex fluid that modulates the host immune response. In addition, hormonal factors modulate the host immune response, impacting the susceptibility to infections. Thus, to assess the impact of androgens and salivary proteins of sand fly vectors on the mast cell (MC) response to Leishmania infections, we infected orchiectomized male mice with the parasite in the presence or absence of sand fly salivary proteins and analyzed the inflammatory response of MCs. Our results showed a differential MC response to the parasite and to vector salivary proteins in mice deprived of gonadal hormones, as compared to sham-operated mice. Orchidectomy induced a different pattern of activation in MC of animals infected with Leishmania and vector-salivary proteins. Our results show that during Leishmania infection, androgens modulate the innate immunity response against the parasite and salivary proteins of the sand fly vector.


Parasitology ◽  
2018 ◽  
Vol 145 (10) ◽  
pp. 1336-1353 ◽  
Author(s):  
Erich Loza Telleria ◽  
Andrea Martins-da-Silva ◽  
Antonio Jorge Tempone ◽  
Yara Maria Traub-Csekö

AbstractIn this review, we explore the state-of-the-art of sand fly relationships with microbiota, viruses and Leishmania, with particular emphasis on the vector immune responses. Insect-borne diseases are a major public health problem in the world. Phlebotomine sand flies are proven vectors of several aetiological agents including viruses, bacteria and the trypanosomatid Leishmania, which are responsible for diseases such as viral encephalitis, bartonellosis and leishmaniasis, respectively. All metazoans in nature coexist intimately with a community of commensal microorganisms known as microbiota. The microbiota has a fundamental role in the induction, maturation and function of the host immune system, which can modulate host protection from pathogens and infectious diseases. We briefly review viruses of public health importance present in sand flies and revisit studies done on bacterial and fungal gut contents of these vectors. We bring this information into the context of sand fly development and immune responses. We highlight the immunity mechanisms that the insect utilizes to survive the potential threats involved in these interactions and discuss the recently discovered complex interactions among microbiota, sand fly, Leishmania and virus. Additionally, some of the alternative control strategies that could benefit from the current knowledge are considered.


Author(s):  
Heloisa D’Avila ◽  
Núbia Pereira de Souza ◽  
Ana Luíza da Silva Albertoni ◽  
Laíris Cunha Campos ◽  
Pollianne Garbero Rampinelli ◽  
...  

Chagas disease is a major public health problem, especially in the South and Central America region. Its incidence is related to poverty and presents a high rate of morbidity and mortality. The pathogenesis of Chagas disease is complex and involves many interactive pathways between the hosts and the Trypanosoma cruzi. Several factors have been implicated in parasite-host interactions, including molecules secreted by infected cells, lipid mediators and most recent, extracellular vesicles (EVs). The EVs of T. cruzi (EVsT) were reported for the first time in the epimastigote forms about 42 years ago. The EVsT are involved in paracrine communication during the infection and can have an important role in the inflammatory modulation and parasite escape mechanism. However, the mechanisms by which EVs employ their pathological effects are not yet understood. The EVsT seem to participate in the activation of macrophages via TLR2 triggering the production of cytokines and a range of other molecules, thus modulating the host immune response which promotes the parasite survival. Moreover, new insights have demonstrated that EVsT induce lipid body formation and PGE2 synthesis in macrophages. This phenomenon is followed by the inhibition of the synthesis of pro-inflammatory cytokines and antigen presentation, causing decreased parasitic molecules and allowing intracellular parasite survival. Therefore, this mini review aims to discuss the role of the EVs from T. cruzi as well as its involvement in the mechanisms that regulate the host immune response in the lipid metabolism and its significance for the Chagas disease pathophysiology.


2018 ◽  
Vol 4 (4) ◽  
pp. 513
Author(s):  
Rakhshan .

Mosquitoes are vectors of many pathogens which causes serious human diseases like Malaria, Filariasis, Japanese encephalitis, Dengue fever, Chikungunya, Yellow fever and Zika virus which constitute a major public health problem globally. Mosquito borne diseases cause high level of economic impact all over the world and result in millions of death every year. They infect around 700,000,000 people annually worldwide and 40,000,000 only in India. The continuous use of synthetic pesticides to control vector mosquitoes has caused physiological resistance, toxic effect on human health, environmental pollution and addition to these, its adverse effects can be observed on non-target organisms. Synthetic chemical pesticides have been proved to be effective, but overall in last 5 decades indiscriminate use of synthetic pesticides against vector borne disease control have originated several ecological issues due to their residual accumulation and development of resistance in target vectors and their chronic effects.


Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 281
Author(s):  
Cassidy Anderson ◽  
Catherine A. Brissette

Lyme disease (LD) has become the most common vector-borne illness in the northern hemisphere. The causative agent, Borrelia burgdorferi sensu lato, is capable of establishing a persistent infection within the host. This is despite the activation of both the innate and adaptive immune responses. B. burgdorferi utilizes several immune evasion tactics ranging from the regulation of surface proteins, tick saliva, antimicrobial peptide resistance, and the disabling of the germinal center. This review aims to cover the various methods by which B. burgdorferi evades detection and destruction by the host immune response, examining both the innate and adaptive responses. By understanding the methods employed by B. burgdorferi to evade the host immune response, we gain a deeper knowledge of B. burgdorferi pathogenesis and Lyme disease, and gain insight into how to create novel, effective treatments.


2007 ◽  
Vol 15 (1-2) ◽  
pp. 5-9
Author(s):  
Attila Fenyvesi

Background: The genetic alterations in colorectal cancer (CRC) progression are determined by two separate pathways, chromosomal and microsatellite instability (MSI). The CRCs with MSI have distinct clinicopathological characteristics with pronounced tumor-associated immune responses. The aim of our study was to investigate the intensity of host immune response in CRC tissue by comparing microsatellite stable (MSS) and instable tumors. Methods: The study was performed on CRC specimens from 28 patients with MSI and compared with 30 MSS tumors. The microsatellite status was evaluated with two markers by PCR and melting point analysis. The immunostaining with anti-CD3 pan-T cell antibody was used to quantify the number of tumor infiltrating lymphocytes. The lymphocytes in peritumoral stromal and the Crohn?s-like peritumoral reaction were counted on H&E slides. Results: No significant differences were found in the average number of lymphocytes in peritumoral stroma and in clinicopathological characteristics of CRCs. The conspicuous Crohn?s-like lymphoid reactions were present in 67.86% of CRCs with MSI versus 26.66% of MSS cases. The CRCs with MSI cases carried significantly higher numbers of tumor infiltrating T-lymphocytes (13.21 versus 7.47) (p<0.0001). Conclusion: The presences of peritumoral Crohn?s-like lymphoid and intraepithelial lymphocytic reaction were intensive markers for MSI in colorectal carcinomas in our study. The peculiar genetic instability in MSI tumors may lead to a continuous production of abnormal peptides, which act as neoantigens. They could induce specific antitumor immune responses effective in limiting tumor growth and spread. Abnormal peptides are potentially promising in immunotherapy advancing and in the design of a vaccine against colorectal tumors with MSI.


2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Evangelia A Pavlatou

The transmission of a wide range of diseases, related to the infection by pathogenic microorganisms is a major public health problem that daily endangers the safety of human population. Silver has been thoroughly studied and used against bacteria due to its antimicrobial properties. Nanostructured silver gathers all the advantages of the silver itself, as well as the advanced performance of the nanomaterials. Thus, currently, silver nanoparticles constitute the most widely used kind of nanoparticles in biomedicine, due to their attractive antimicrobial properties. A variety of physical and chemical methods are employed for the AgNPs synthesis. However, many of them include the use of toxic reagents or require large amounts of energy, during the synthesis process. For this reason, many eco-friendly methods are proposed in order to synthesize AgNPs. Hence, biogenic synthesis of AgNPs, utilizing biological resources opens a novel route for the development of alternative production processes.These methods seem to have significant advantages, as the extracts contribute positively to the formation and enhancement of the antimicrobial activity of AgNPs, also acting as protective agents of the produced particles. In this review an integrated approach of AgNPs bio-synthetic methods using microorganisms, such as bacteria and fungi, plants and plant extracts, as well as several templates, like DNA and viruses is discussed, shedding light on the comparative advantages of them.


2014 ◽  
Author(s):  
Bishwajit Ghose ◽  
Cheng Zhaohui ◽  
He Zhifei

South Asian population suffer a particularly wide range of infectious diseases among which TB and HIV appear to produce most profound influence across various dimensions of social life, healthcare and the economy. Although the countries in this region have a relatively lower prevalence of HIV/AIDS compared to other developing regions until now, the future looks rather bleak in terms of preparedness for emerging healthcare realities. Tuberculosis on the other hand, has always been a major public health problem plaguing the healthcare system and the economy for decades. Moreover, the emergence of the drug resistant (MDR-TB & XDR-TB) strains are making the existing intervention and prevention strategies less effective and posing ever-growing threats to the underdeveloped healthcare infrastructure. Understanding the underlying social-determinants of these diseases can prove crucial to design more comprehensive intervention approaches. This article aims to clarify why the healthcare system in South Asia needs to adopt a social-determinants-of-health (SDOH) approach as a long-term strategy for more efficient prevention and control of TB and HIV infection.


Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 989
Author(s):  
Alexey A. Lozhkov ◽  
Sergey A. Klotchenko ◽  
Edward S. Ramsay ◽  
Herman D. Moshkoff ◽  
Dmitry A. Moshkoff ◽  
...  

Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection.


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