The skin as interface in the transmission of arthropod-borne pathogens

Frischknecht, Friedrich

doi:10.1111/j.1462-5822.2007.00955.x

Cited by 49 publications

(34 citation statements)

References 106 publications

(126 reference statements)

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“…Vector-borne infections that are initiated in the skin are likely to involve adaptations to this unique microenvironment by the invading pathogen (29). Bypassing or altering this initial step in infection is likely to have significant and unforeseen consequences, such as those observed here.…”

Section: Discussionmentioning

confidence: 87%

“…Vaccination by different routes has also been shown to influence the efficacy of vaccines against parasitic, bacterial, and viral infections, as well as cancer (3,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). In the case of infections initiated in the skin by the bite of an insect vector, such as Yersinia, Plasmodium, Borrelia, and Leishmania infections (29), the use of an intradermal route of infection would appear to be critical, since the initial interaction between these pathogens and the host takes place primarily in the skin under natural conditions (11,15,(30)(31)(32). However, the factors that determine site-or route-specific influences on infection or vaccination remain poorly defined.…”

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confidence: 99%

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Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

et al. 2014

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Section: Discussionmentioning

confidence: 87%

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confidence: 99%

Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

et al. 2014

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“…The advent of mouse-human chimeras, especially those with transplanted human hematopoietic stem cells, allowed the generation of the first animal model of dengue fever (8). The hu-NSG mice that we have worked with more recently (37,38) and reported here have functional human T, B, and NK cells, along with other cells of the immune system (monocytes/macrophages, neutrophils, and mast and dendritic cells) (14,30,56,58) that reside in human epithelium and capillaries, the targets of mosquito bites (24) and DENV infection (11,15,36,62). However, hu-NSG mice lack other possible human target cells, such as hepatocytes and endothelial cells, and do not secrete human complement factors that could modify infection or disease (6).…”

Section: Discussionmentioning

confidence: 99%

Mosquito Bite Delivery of Dengue Virus Enhances Immunogenicity and Pathogenesis in Humanized Mice

Cox

Mota

Sukupolvi-Petty

et al. 2012

J Virol

184

205

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bDengue viruses (DENV) are transmitted to humans by the bite of Aedes aegypti or Aedes albopictus mosquitoes, with millions of infections annually in over 100 countries. The diseases they produce, which occur exclusively in humans, are dengue fever (DF) and dengue hemorrhagic fever (DHF). We previously developed a humanized mouse model of DF in which mice transplanted with human hematopoietic stem cells produced signs of DENV disease after injection with low-passage, wild-type isolates. Using these mice, but now allowing infected A. aegypti to transmit dengue virus during feeding, we observed signs of more severe disease (higher and more sustained viremia, erythema, and thrombocytopenia). Dengue fever (DF) in humans is characterized by fever, myalgia, arthralgia, abdominal pain, rash, low platelet counts (thrombocytopenia), and a viremia that begins 3 to 4 days after infection by mosquito bite. The more severe form of dengue, dengue hemorrhagic fever (DHF), usually presents as a second phase of disease, at the end of the fever stage, but with a sudden onset of plasma leakage that can result in hemoconcentration, pleural effusion, ascites, shock, hepatic failure, and encephalopathy. While this hemodynamic syndrome can resolve in 2 days, complete convalescence can take weeks to months (reviewed in reference 53). Moreover, ϳ5% of DHF patients die, usually from hypotensive shock, due to a delay in the recognition and treatment of the plasma leakage. Dengue virus (DENV)-induced disease has increased markedly due to the global spread of the virus and expansion of its mosquito vectors, and it is now the most important viral illness transmitted by insects (61). However, a clear understanding of the mechanisms leading to DF and DHF has been limited by several factors: (i) inadequate animal models of disease, with most knowledge being derived from clinical studies and in vitro experiments; (ii) the genetic diversity of DENV, with four different antigenic groups or serotypes and with humans potentially infected multiple times; and (iii) the relative risk of severe DENV disease, which is enhanced greatly by secondary infection with a heterologous serotype. The last factor has prompted the development of several models of immunopathogenesis (reviewed in reference 47) that have been difficult to evaluate experimentally, given the absence of reliable immunocompetent-animal models of human disease presenting with clinical signs of DHF after serial infection with wild-type viruses.We sought to produce an animal model of disease that could mimic the natural cycle of mosquito-human transmission with low-passage-number viruses from clinical samples, using human cells as targets of infection within a neutral background of nonsusceptible tissues (mouse) and using the appropriate species of mosquito vector, to evaluate the influence of biting/probing, virus delivery, and saliva proteins on DENV pathogenesis. Using humanized NOD/SCID/interleukin 2 receptor gamma (IL-2R␥)-null (hu-NSG) mice that had previously defined differences in th...

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“…The epidermis is the outermost layer of the skin and constitutes a strong physical barrier that pathogens must cross to enter the body. Pathogens that survive in bloodfeeding arthropods can cross this layer through the mechanical action of the arthropod's probing mouth parts (4). Consequently, the dermis, located immediately adjacent to the epidermis, is highly exposed to these pathogens.…”

mentioning

confidence: 99%

Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to the Dermis

et al. 2015

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H ost-pathogen interactions begin with transmission and continue as the pathogen disseminates into deeper tissues. These tissues are in themselves microenvironments with defined immunological characteristics and can serve as barriers to prevent spread. For arthropod-borne pathogens, the skin epithelium is the first barrier that must be surpassed to penetrate into deeper organs (1, 2). The complexity of the immune responses of each layer of the skin reflects the specificity at which this tissue can act upon invaders.Based on its histological architecture, the skin can be divided into three main layers, namely, epidermis, dermis, and subcutaneous space (also known as hypodermis) (3). Each layer encompasses not only specific architectural qualities but also unique immunological characteristics that define them (2). How these characteristics influence the progression of infection is unknown. The epidermis is the outermost layer of the skin and constitutes a strong physical barrier that pathogens must cross to enter the body. Pathogens that survive in bloodfeeding arthropods can cross this layer through the mechanical action of the arthropod's probing mouth parts (4). Consequently, the dermis, located immediately adjacent to the epidermis, is highly exposed to these pathogens. Because most arthropod vectors do not penetrate beyond the dermis to the subcutaneous (s.c.) space, the dermis is, most likely, the first tissue where initial host-pathogen interactions occur during vector-borne infections (1,(5)(6)(7).Yersinia pestis is a Gram-negative bacterium and the causative agent of plague. This highly virulent pathogen was responsible for major pandemics in history and continues to survive in animal reservoirs in many parts of the world (8, 9). Bubonic plague is the most prevalent form of the disease and occurs after bacterial inoculation into the skin, typically by a flea vector (10). From the skin, Y. pestis disseminates to draining lymph nodes (LNs) via lymphatic vessels (11) and then to deeper organs through the bloodstream (12). Systemic dissemination results in septic shock, severe organ failure, and death.Models of infection that target the s.c. space are broadly used in plague research (13-16) as this is a relatively easy tissue to target. However, the dermis is strongly implicated as the layer of the skin probed by fleas during transmission (5, 17). In comparison with s.c. models, intradermal (i.d.) inoculations require more dexterity and can be more challenging to implement in biosafety level three facilities, which are mandatory when handling fully virulent strains of Y. pestis. In this study, we further characterize the i.d. model we used in a previous study (11) and compare i.d. and s.c. inoculations to investigate whether infection model impacts progression of bubonic plague. We found substantial differences in disease progression after inoculation by the two different routes. In addition, we found that dissemination of bacteria from the LNs is restricted. These findings are relevant for the understanding ...

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The skin as interface in the transmission of arthropod-borne pathogens

Cited by 49 publications

References 106 publications

Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

Mosquito Bite Delivery of Dengue Virus Enhances Immunogenicity and Pathogenesis in Humanized Mice

Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to the Dermis

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