scholarly journals Insulin potentiates JAK/STAT signaling to broadly inhibit flavivirus replication in insect vectors

2019 ◽  
Author(s):  
Laura R.H. Ahlers ◽  
Chasity E. Trammell ◽  
Grace F. Carrell ◽  
Sophie Mackinnon ◽  
Brandi K. Torrevillas ◽  
...  

SUMMARYThe World Health Organization estimates that over half of the world’s population is at risk for vector-borne diseases, such as those caused by arboviral infection. Because many arboviruses are mosquito-borne, investigation of the insect immune response will help identify targets that could reduce the spread of these viruses by the mosquito. In this study, we used a genetic screening approach to identify insulin-like receptor as a novel component of the immune response to arboviral infection. We determined that vertebrate insulin reduces West Nile virus (WNV) replication in Drosophila melanogaster as well as WNV, Zika, and dengue virus titers in mosquito cells. Mechanistically, we showed that insulin signaling activates the JAK/STAT, but not RNAi, pathway to control infection. Finally, we validated that insulin priming of adult female Culex mosquitoes through a blood meal reduces WNV infection, demonstrating an essential role for insulin signaling in insect antiviral responses to emerging human pathogens.

2020 ◽  
Vol 63 (4) ◽  
pp. 7-18 ◽  
Author(s):  
Anamary Súarez Reyes ◽  
Carlos Agustín Villegas Valverde

Characteristics and Specialization of the Immune Response in COVID-19 Abstract The outbreak of coronavirus pneumonia in Wuhan, China, became a pandemic on March 11, 2020. It has caused almost 4 million confirmed cases worldwide, with more than 270,000 deaths. Coronavirus is an enveloped RNA virus of the β-coronavirus genus distributed in birds, humans, and other mammals. The World Health Organization has named the new disease COVID-19. The scientific community is look http://doi.org/10.22201/fm.24484865e.2020.63.4.02 8 8 Revista de la Facultad de Medicina de la UNAM | ing for evidence that can lead to a better understanding of the infection and the immune response (IR), prognostic and therapeutic predictors, effective treatments and vaccines. The objective of this review was to compile updated scientific evidence of the IR to COVID-19, in order to guide professionals with solutions that have a clinical impact. The most important elements involve innate immunity with failures in the interferon system in the early stages of the infection and a sustained increase in proinflammatory interleukins. This can end in a potentially fatal cytokine storm. The infiltration of neutrophils and macrophages at the alveolar level, accompanied by neutrophilia, is very characteristic. Lymphopenia is evident at the adaptive immunity level, that, depending on the degree, can indicate the severity of the disease. Understanding the temporal sequence of the IR is crucial for choosing the appropriate and effective therapies, especially when selecting which type of anti-inflammatory drugs can be used and the frequency of the dosage. Due to the fact that it is difficult to determine when they will be clearly beneficial, not harmful to the IR and not too late, due to the irreversibility of the process. Key words: COVID-19; coronavirus; immune response


Author(s):  
Mara Moreno-Gómez ◽  
Rubén Bueno-Marí ◽  
Andrea Drago ◽  
Miguel A Miranda

Abstract Vector-borne diseases are a worldwide threat to human health. Often, no vaccines or treatments exist. Thus, personal protection products play an essential role in limiting transmission. The World Health Organization (WHO) arm-in-cage (AIC) test is the most common method for evaluating the efficacy of topical repellents, but it remains unclear whether AIC testing conditions recreate the mosquito landing rates in the field. This study aimed to estimate the landing rate outdoors, in an area of Europe highly infested with the Asian tiger mosquito (Aedes albopictus (Skuse, 1894, Diptera: Culididae)), and to determine how to replicate this rate in the laboratory. To assess the landing rate in the field, 16 individuals were exposed to mosquitoes in a highly infested region of Italy. These field results were then compared to results obtained in the laboratory: 1) in a 30 m3 room where nine volunteers were exposed to different mosquito abundances (ranges: 15–20, 25–30, and 45–50) and 2) in a 0.064 m3 AIC test cage where 10 individuals exposed their arms to 200 mosquitoes (as per WHO requirements). The highest mosquito landing rate in the field was 26.8 landings/min. In the room test, a similar landing rate was achieved using 15–20 mosquitoes (density: 0.50–0.66 mosquitoes/m3) and an exposure time of 3 min. In the AIC test using 200 mosquitoes (density: 3,125 mosquitoes/m3), the landing rate was 229 ± 48 landings/min. This study provides useful reference values that can be employed to design new evaluation standards for topical repellents that better simulate field conditions.


The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. In a recent study of Nanshan Chen et al., on patients of Wuhan Jinyintan Hospital, Wuhan, China, from the 99 patients with SARSCoV-2 infection, 51% had chronic diseases and they had symptoms of fever (83%), cough (82%) shortness of breath (31%), muscle ache (11%), fatigue (9%), headache (8%), sore throat (5%), rhinorrhea (4%), chest pain (2%), diarrhea (2%), and nausea and vomiting (1%) [1, 2]. The majority of patients can recover, however, about 25% of patients will progress into severe complications including acute respiratory distress syndrome (ARDS), which may worsen rapidly into respiratory failure, need an intensive care unit (ICU) and even cause multiple organ failure [3]. Depending on the pathophysiological mechanisms supposed to be involved in the development of the various clinical forms of the disease, various types of treatment have been tested with varying degrees of success. We have developed a nanotherapy to block the entry of the virus into the host cell, to reduce its potential for replication and to regulate the immune response against the microbial aggressor [4].


Author(s):  
A. D. Cliff ◽  
M.R. Smallman-Raynor ◽  
P. Haggett ◽  
D.F. Stroup ◽  
S.B. Thacker

In this and the next four chapters, we examine five change agents which have facilitated the emergence and re-emergence of infectious human diseases. Each agent—microbial and genetic adaptation, technology and industry, changes in host populations, environmental and ecological change, and war as a disease amplifier—has underpinned over the centuries both the appearance of new diseases and the waxing and waning of familiar infections. As shown in Figure II.1, the agents are not independent and commonly interact in complex ways to facilitate microbe emergence and re-emergence at different times and in different geographical locations. Accordingly, we also explore these interactions in our account. We begin here with microbial and vector adaptation. Disease microbes are in a continuous state of evolution, responding and adapting to the challenges and opportunities afforded by their hosts and their environments (Morse 1995). New pathogens are evolving, old pathogens are developing enhanced virulence and new clinical expressions, and susceptible pathogens are acquiring resistance to antimicrobial agents. In parallel, the environmental tolerance bands of both old and new pathogens are also changing (Cohen 1998). Not only are disease microbes in a continuous state of evolution. So, too, are the arthropod vectors that transmit many human pathogens. In the second half of the twentieth century, many of these vectors have developed tolerance to an expanding range of insecticides, larvicides, pupicides, and other chemical agents used in their control (World Health Organization 1992c). Against this background, our examination of microbial change and vector adaptation is structured around the three interlinked themes shown in Figure 4.1. We begin in Section 4.2 by examining the issue of natural variation in pathogens and illustrate this with special reference to the emergence and spread of novel subtypes of influenza A virus. We then examine the topic of selective pressure and genetic change in the context of the man-made problems of pathogen resistance to antimicrobials (Section 4.3) and vector resistance to insecticides (Section 4.4). The processes of microbial change and vector adaptation are not intrinsically geographical but they take place within, and are inextricably linked to, specific geographical environments. This gives a strong geographical emphasis to our discussion.


Author(s):  
Emily Chan ◽  
Tiffany Sham ◽  
Tayyab Shahzada ◽  
Caroline Dubois ◽  
Zhe Huang ◽  
...  

Climate change is expanding the global at-risk population for vector-borne diseases (VBDs). The World Health Organization (WHO) health emergency and disaster risk management (health-EDRM) framework emphasises the importance of primary prevention of biological hazards and its value in protecting against VBDs. The framework encourages stakeholder coordination and information sharing, though there is still a need to reinforce prevention and recovery within disaster management. This keyword-search based narrative literature review searched databases PubMed, Google Scholar, Embase and Medline between January 2000 and May 2020, and identified 134 publications. In total, 10 health-EDRM primary prevention measures are summarised at three levels (personal, environmental and household). Enabling factor, limiting factors, co-benefits and strength of evidence were identified. Current studies on primary prevention measures for VBDs focus on health risk-reduction, with minimal evaluation of actual disease reduction. Although prevention against mosquito-borne diseases, notably malaria, has been well-studied, research on other vectors and VBDs remains limited. Other gaps included the limited evidence pertaining to prevention in resource-poor settings and the efficacy of alternatives, discrepancies amongst agencies’ recommendations, and limited studies on the impact of technological advancements and habitat change on VBD prevalence. Health-EDRM primary prevention measures for VBDs require high-priority research to facilitate multifaceted, multi-sectoral, coordinated responses that will enable effective risk mitigation.


2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Áurea Gabriel ◽  
Ana Valério-Bolas ◽  
Joana Palma-Marques ◽  
Patrícia Mourata-Gonçalves ◽  
Pedro Ruas ◽  
...  

This review is aimed at providing a comprehensive outline of the immune response displayed against cutaneous leishmaniasis (CL), the more common zoonotic infection caused by protozoan parasites of the genus Leishmania. Although of polymorphic clinical presentation, classically CL is characterized by leishmaniotic lesions on the face and extremities of the patients, which can be ulcerative, and even after healing can lead to permanent injuries and disfigurement, affecting significantly their psychological, social, and economic well-being. According a report released by the World Health Organization, the disability-adjusted life years (DALYs) lost due to leishmaniasis are close to 2.4 million, annually there are 1.0–1.5 million new cases of CL, and a numerous population is at risk in the endemic areas. Despite its increasing worldwide incidence, it is one of the so-called neglected tropical diseases. Furthermore, this review provides an overview of the existing knowledge of the host innate and acquired immune response to cutaneous species of Leishmania. The use of animal models and of in vitro studies has improved the understanding of parasite-host interplay and the complexity of immune mechanisms involved. The importance of diagnosis accuracy associated with effective patient management in CL reduction is highlighted. However, the multiple factors involved in CL epizoology associated with the unavailability of vaccines or drugs to prevent infection make difficult to formulate an effective strategy for CL control.


2020 ◽  
Vol 11 ◽  
Author(s):  
Concetta Di Natale ◽  
Sara La Manna ◽  
Ilaria De Benedictis ◽  
Paola Brandi ◽  
Daniela Marasco

At the end of December 2019, an epidemic form of respiratory tract infection now named COVID-19 emerged in Wuhan, China. It is caused by a newly identified viral pathogen, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which can cause severe pneumonia and acute respiratory distress syndrome. On January 30, 2020, due to the rapid spread of infection, COVID-19 was declared as a global health emergency by the World Health Organization. Coronaviruses are enveloped RNA viruses belonging to the family of Coronaviridae, which are able to infect birds, humans and other mammals. The majority of human coronavirus infections are mild although already in 2003 and in 2012, the epidemics of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV), respectively, were characterized by a high mortality rate. In this regard, many efforts have been made to develop therapeutic strategies against human CoV infections but, unfortunately, drug candidates have shown efficacy only into in vitro studies, limiting their use against COVID-19 infection. Actually, no treatment has been approved in humans against SARS-CoV-2, and therefore there is an urgent need of a suitable vaccine to tackle this health issue. However, the puzzled scenario of biological features of the virus and its interaction with human immune response, represent a challenge for vaccine development. As expected, in hundreds of research laboratories there is a running out of breath to explore different strategies to obtain a safe and quickly spreadable vaccine; and among others, the peptide-based approach represents a turning point as peptides have demonstrated unique features of selectivity and specificity toward specific targets. Peptide-based vaccines imply the identification of different epitopes both on human cells and virus capsid and the design of peptide/peptidomimetics able to counteract the primary host-pathogen interaction, in order to induce a specific host immune response. SARS-CoV-2 immunogenic regions are mainly distributed, as well as for other coronaviruses, across structural areas such as spike, envelope, membrane or nucleocapsid proteins. Herein, we aim to highlight the molecular basis of the infection and recent peptide-based vaccines strategies to fight the COVID-19 pandemic including their delivery systems.


2018 ◽  
Vol 10 (7) ◽  
pp. 148 ◽  
Author(s):  
Elkin Navarro-Quiroz ◽  
Roberto Navarro-Quiroz ◽  
Pierine España-Puccini ◽  
José Luis Villarreal ◽  
Anderson Díaz Perez ◽  
...  

Helicobacter pylori (H. pylori) is classified by the World Health Organization (WHO) as a group I carcinogen and is one of the most efficient human pathogens with over half of the world's population colonized by this gram-negative spiral bacterium. H. pylori can cause a chronic infection in the stomach during early childhood that persists throughout life due to diverse mechanisms of immune response evasion. H. pylori has several factors strongly associated with increased risk of disease such as toxins, adhesins, and chemoattractants, some of which are highly polymorphic, phase variable, and have different functions. Conventional treatments involve the use of antibiotics. However, treatment frequently fails due to the resistance H. pylori has progressively developed to antibiotics. This creates the need for different treatments made possible by identifying new therapeutic targets in the pathogen’s genome.The purpose of this study was an in silico prediction of T- and B- epitopes in H. pylori proteins. Twenty-two external membrane proteins from H. pylori Strain 26695 (accession number NC_000915) were identified using the web tool Vaxign (http://www.violinet.org/vaxign/). A total of one-hundred epitopes (60 class I epitopes and 40 class II epitopes) that could be used to develop novel non-antibiotics drugs for an H. pylori infection were predicted.


Author(s):  
Antonio Ligsay ◽  
Olivier Telle ◽  
Richard Paul

Cities worldwide are facing ever-increasing pressure to develop mitigation strategies for all sectors to deal with the impacts of climate change. Cities are expected to house 70% of the world’s population by 2050 and developing related resilient health systems is a significant challenge. Because of their physical nature, cities’ surface temperatures are often substantially higher than that of the surrounding rural areas, generating the so-called Urban Heat Island (UHI) effect. Whilst considerable emphasis has been placed on strategies to mitigate against the UHI-associated negative health effects of heat and pollution, the World Health Organization estimates that one of the main consequences of global warming will be an increased burden of such vector-borne diseases. Many of the major mosquito-borne diseases are urban and thus the global population exposed to these pathogens will steadily increase. Mitigation strategies beneficial for one sector may, however, be detrimental for another. Implementation of inter-sectoral strategies that can benefit many sectors (such as water, labour and health) do exist and would enable optimal use of the meagre resources available. Discussion among inter-sectoral stakeholders should be actively encouraged.


2021 ◽  
Vol 16 (10) ◽  
pp. 189-197
Author(s):  
Manpreet Kaur ◽  
Rajinder Kaur ◽  
Reena Gupta

The beginning of year 2020 has brought with it mass destruction of mankind in form of novel coronavirus, named as CoVID-19. Declared as pandemic by World Health Organization (WHO), CoVID-19 has its origin in bats and pangolin from which it was probably transferred to human. Subsequent human to human transmission has been seen by respiratory droplets, fomites and oral-fecal route. The disease has caused widespread deaths in America, China, France and Italy followed by many European and Asian countries. CoVID-19 targets the human lungs and multiplies in alveoli using host machinery. Interstitial edema and alveolar edema at later stages cause alveoli collapse and difficulty in breathing. Severe cases may pave to systemic inflammatory response that has fatal response in body. Unfortunately, researchers are still struggling for potential vaccine or promising drug to combat the disease. WHO has issued guidelines suggesting regular hand washing, social distancing, wearing masks and quarantination as the best ways to prevent infection. This review gives an overview of the novel CoVID-19, conditions and immune response of human body related with it.


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