A thrombomodulin mutation that impairs active protein C generation is detrimental in severe pneumonia-derived gram-negative sepsis (melioidosis).

Abstract:

BACKGROUND:During severe (pneumo)sepsis inflammatory and coagulation pathways become activated as part of the host immune response. Thrombomodulin (TM) is involved in a range of host defense mechanisms during infection and plays a pivotal role in activation of protein C (PC) into active protein C (APC). APC has both anticoagulant and anti-inflammatory properties. In this study we investigated the effects of impaired TM-mediated APC generation during melioidosis, a common form of community-acquired Gram-negative (pneumo)sepsis in South-East Asia caused by Burkholderia (B.) pseudomallei. METHODOLOGY/PRINCIPAL FINDINGS:(WT) mice and mice with an impaired capacity to activate protein C due to a point mutation in their Thbd gene (TMpro/pro mice) were intranasally infected with B. pseudomallei and sacrificed after 24, 48 or 72 hours for analyses. Additionally, survival studies were performed. When compared to WT mice, TMpro/pro mice displayed a worse survival upon infection with B. pseudomallei, accompanied by increased coagulation activation, enhanced lung neutrophil influx and bronchoalveolar inflammation at late time points, together with increased hepatocellular injury. The TMpro/pro mutation had limited if any impact on bacterial growth and dissemination. CONCLUSION/SIGNIFICANCE:TM-mediated protein C activation contributes to protective immunity after infection with B. pseudomallei. These results add to a better understanding of the regulation of the inflammatory and procoagulant response during severe Gram-negative (pneumo)sepsis.

journal_name

PLoS Negl Trop Dis

authors

Kager LM,Wiersinga WJ,Roelofs JJ,de Boer OJ,Weiler H,van 't Veer C,van der Poll T

doi

10.1371/journal.pntd.0002819

subject

Has Abstract

pub_date

2014-04-24 00:00:00

pages

e2819

issue

4

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-13-01029

journal_volume

8

pub_type

杂志文章
  • Comparing models for early warning systems of neglected tropical diseases.

    abstract:BACKGROUND:Early warning systems (EWS) are management tools to predict the occurrence of epidemics of infectious diseases. While climate-based EWS have been developed for malaria, no standard protocol to evaluate and compare EWS has been proposed. Additionally, there are several neglected tropical diseases whose transm...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000033

    authors: Chaves LF,Pascual M

    更新日期:2007-10-22 00:00:00

  • Pyrethroid resistance persists after ten years without usage against Aedes aegypti in governmental campaigns: Lessons from São Paulo State, Brazil.

    abstract:BACKGROUND:Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is found at high densities in tropical urban areas. The dissemination of this vector is partially the consequence of failures in current vector control methods, still mainly relying upon insecticides. In the State of São Paulo (SP), Brazil, publi...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0006390

    authors: Macoris ML,Martins AJ,Andrighetti MTM,Lima JBP,Valle D

    更新日期:2018-03-30 00:00:00

  • Healthcare demand in response to rabies elimination campaigns in Latin America.

    abstract::The World Health Organization, the World Organization for Animal Health, and the Food and Agriculture Organization have resolved to eliminate human rabies deaths due to dog bites by 2030, and the Vaccine Alliance (Gavi) has added human rabies vaccines to their investments for 2021-2025. Implementing these goals cost-e...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0007630

    authors: Yoder J,Younce E,Lankester F,Palmer GH

    更新日期:2019-09-26 00:00:00

  • Auranofin is highly efficacious against Toxoplasma gondii in vitro and in an in vivo experimental model of acute toxoplasmosis.

    abstract:BACKGROUND:The mainstay of toxoplasmosis treatment targets the folate biosynthetic pathways and has not changed for the last 50 years. The activity of these chemotherapeutic agents is restricted to one lifecycle stage of Toxoplasma gondii, they have significant toxicity, and the impending threat of emerging resistance ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0002973

    authors: Andrade RM,Chaparro JD,Capparelli E,Reed SL

    更新日期:2014-07-31 00:00:00

  • Evaluation of Chikungunya diagnostic assays: differences in sensitivity of serology assays in two independent outbreaks.

    abstract:BACKGROUND:The sensitivity and specificity of two in-house MAC-ELISA assays were tested and compared with the performance of commercially-available CTK lateral flow rapid test and EUROIMMUN IFA assays for the detection of anti-Chikungunya virus (CHIKV) IgM. Each MAC-ELISA assay used a whole virus-based antigen derived ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000753

    authors: Yap G,Pok KY,Lai YL,Hapuarachchi HC,Chow A,Leo YS,Tan LK,Ng LC

    更新日期:2010-07-20 00:00:00

  • Visceral leishmaniasis and HIV coinfection in the Mediterranean region.

    abstract::Visceral leishmaniasis is hypoendemic in Mediterranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%-6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pntd.0003021

    authors: Monge-Maillo B,Norman FF,Cruz I,Alvar J,López-Vélez R

    更新日期:2014-08-21 00:00:00

  • Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases.

    abstract:BACKGROUND:Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolution using n...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0005598

    authors: Stefani MMA,Avanzi C,Bührer-Sékula S,Benjak A,Loiseau C,Singh P,Pontes MAA,Gonçalves HS,Hungria EM,Busso P,Piton J,Silveira MIS,Cruz R,Schetinni A,Costa MB,Virmond MCL,Diorio SM,Dias-Baptista IMF,Rosa PS,Matsuoka M

    更新日期:2017-06-15 00:00:00

  • PARK2 mediates interleukin 6 and monocyte chemoattractant protein 1 production by human macrophages.

    abstract::Leprosy is a persistent infectious disease caused by Mycobacterium leprae that still affects over 200,000 new patients annually. The host genetic background is an important risk factor for leprosy susceptibility and the PARK2 gene is a replicated leprosy susceptibility candidate gene. The protein product of PARK2, Par...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0002015

    authors: de Léséleuc L,Orlova M,Cobat A,Girard M,Huong NT,Ba NN,Thuc NV,Truman R,Spencer JS,Adams L,Thai VH,Alcais A,Schurr E

    更新日期:2013-01-01 00:00:00

  • A non mouse-adapted dengue virus strain as a new model of severe dengue infection in AG129 mice.

    abstract::The spread of dengue (DEN) worldwide combined with an increased severity of the DEN-associated clinical outcomes have made this mosquito-borne virus of great global public health importance. Progress in understanding DEN pathogenesis and in developing effective treatments has been hampered by the lack of a suitable sm...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000672

    authors: Tan GK,Ng JK,Trasti SL,Schul W,Yip G,Alonso S

    更新日期:2010-04-27 00:00:00

  • Failure of fluconazole in treating cutaneous leishmaniasis caused by Leishmania guyanensis in the Brazilian Amazon: An open, nonrandomized phase 2 trial.

    abstract:BACKGROUND:The treatment of Leishmaniasis caused by Leishmania (Viannia) guyanensis is based on a weak strength of evidence from very few clinical trials and some case series reports. Current treatment guidelines recommend pentamidine isethionate or meglumine antimoniate (Glucantime) as the first-line choices. Both are...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0006225

    authors: Francesconi VA,Francesconi F,Ramasawmy R,Romero GAS,Alecrim MDGC

    更新日期:2018-02-26 00:00:00

  • Characterization of flavivirus infection in salivary gland cultures from male Ixodes scapularis ticks.

    abstract::Infected Ixodes scapularis (black-legged tick) transmit a host of serious pathogens via their bites, including Borrelia burgdorferi, Babesia microti, and tick-borne flaviviruses (TBFVs), such as Powassan virus (POWV). Although the role of female I. scapularis ticks in disease transmission is well characterized, the ro...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0008683

    authors: Kendall BL,Grabowski JM,Rosenke R,Pulliam M,Long DR,Scott DP,Offerdahl DK,Bloom ME

    更新日期:2020-10-05 00:00:00

  • A randomized, single-ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection.

    abstract:BACKGROUND:Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe e...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章,随机对照试验

    doi:10.1371/journal.pntd.0002953

    authors: Awadzi K,Opoku NO,Attah SK,Lazdins-Helds J,Kuesel AC

    更新日期:2014-06-26 00:00:00

  • Prevalence of signs of trachoma, ocular Chlamydia trachomatis infection and antibodies to Pgp3 in residents of Kiritimati Island, Kiribati.

    abstract:OBJECTIVE:In some Pacific Island countries, such as Solomon Islands and Fiji, active trachoma is common, but ocular Chlamydia trachomatis (Ct) infection and trachomatous trichiasis (TT) are rare. On Tarawa, the most populous Kiribati island, both the active trachoma sign "trachomatous inflammation-follicular" (TF) and ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0005863

    authors: Cama A,Müller A,Taoaba R,Butcher RMR,Itibita I,Migchelsen SJ,Kiauea T,Pickering H,Willis R,Roberts CH,Bakhtiari A,Le Mesurier RT,Alexander NDE,Martin DL,Tekeraoi R,Solomon AW,Global Trachoma Mapping Project.

    更新日期:2017-09-12 00:00:00

  • Genetic diversity in two Plasmodium vivax protein ligands for reticulocyte invasion.

    abstract::The interaction between Plasmodium vivax Duffy binding protein (PvDBP) and Duffy antigen receptor for chemokines (DARC) has been described as critical for the invasion of human reticulocytes, although increasing reports of P. vivax infections in Duffy-negative individuals questions its unique role. To investigate the ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0006555

    authors: Roesch C,Popovici J,Bin S,Run V,Kim S,Ramboarina S,Rakotomalala E,Rakotoarison RL,Rasoloharimanana T,Andriamanantena Z,Kumar A,Guillotte-Blisnick M,Huon C,Serre D,Chitnis CE,Vigan-Womas I,Menard D

    更新日期:2018-10-22 00:00:00

  • A research agenda for helminth diseases of humans: basic research and enabling technologies to support control and elimination of helminthiases.

    abstract::Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vecto...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pntd.0001445

    authors: Lustigman S,Geldhof P,Grant WN,Osei-Atweneboana MY,Sripa B,Basáñez MG

    更新日期:2012-01-01 00:00:00

  • Adaptive immunity against Leishmania nucleoside hydrolase maps its c-terminal domain as the target of the CD4+ T cell-driven protective response.

    abstract::Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000866

    authors: Nico D,Claser C,Borja-Cabrera GP,Travassos LR,Palatnik M,Soares IS,Rodrigues MM,Palatnik-de-Sousa CB

    更新日期:2010-11-09 00:00:00

  • Hookworm infection and environmental factors in mbeya region, Tanzania: a cross-sectional, population-based study.

    abstract:BACKGROUND:Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. METHODOLOGY:Cross-sectional interview data and stool s...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0002408

    authors: Riess H,Clowes P,Kroidl I,Kowuor DO,Nsojo A,Mangu C,Schüle SA,Mansmann U,Geldmacher C,Mhina S,Maboko L,Hoelscher M,Saathoff E

    更新日期:2013-09-05 00:00:00

  • Distribution and seasonal fluctuations of Ae. aegypti and Ae. albopictus larval and pupae in residential areas in an urban landscape.

    abstract::Dengue, a vector-borne disease spread by Aedes mosquitoes, is a global threat. In the absence of an efficacious dengue vaccine, vector control is the key intervention tool in Singapore. A good understanding of vector habitats is essential to formulate operational strategies. We examined the distribution, long-term tre...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0008209

    authors: Rajarethinam J,Ong J,Neo ZW,Ng LC,Aik J

    更新日期:2020-04-20 00:00:00

  • Geospatial distribution of intestinal parasitic infections in Rio de Janeiro (Brazil) and its association with social determinants.

    abstract:BACKGROUND:Intestinal parasitic infections remain among the most common infectious diseases worldwide. This study aimed to estimate their prevalence and provide a detailed analysis of geographical distribution of intestinal parasites in the metropolitan region of Rio de Janeiro, considering demographic, socio-economic,...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0005445

    authors: Faria CP,Zanini GM,Dias GS,da Silva S,de Freitas MB,Almendra R,Santana P,Sousa MD

    更新日期:2017-03-08 00:00:00

  • Diagnostic accuracy of five serologic tests for Strongyloides stercoralis infection.

    abstract:BACKGROUND:The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference ("gold") st...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0002640

    authors: Bisoffi Z,Buonfrate D,Sequi M,Mejia R,Cimino RO,Krolewiecki AJ,Albonico M,Gobbo M,Bonafini S,Angheben A,Requena-Mendez A,Muñoz J,Nutman TB

    更新日期:2014-01-09 00:00:00

  • Hookworm infection is associated with decreased CD4+ T cell counts in HIV-infected adult Ugandans.

    abstract::Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretro...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0005634

    authors: Morawski BM,Yunus M,Kerukadho E,Turyasingura G,Barbra L,Ojok AM,DiNardo AR,Sowinski S,Boulware DR,Mejia R

    更新日期:2017-05-25 00:00:00

  • Mosquito vector diversity across habitats in central Thailand endemic for dengue and other arthropod-borne diseases.

    abstract::Recent years have seen the greatest ecological disturbances of our times, with global human expansion, species and habitat loss, climate change, and the emergence of new and previously-known infectious diseases. Biodiversity loss affects infectious disease risk by disrupting normal relationships between hosts and path...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0002507

    authors: Thongsripong P,Green A,Kittayapong P,Kapan D,Wilcox B,Bennett S

    更新日期:2013-10-31 00:00:00

  • Associations between selective attention and soil-transmitted helminth infections, socioeconomic status, and physical fitness in disadvantaged children in Port Elizabeth, South Africa: An observational study.

    abstract:BACKGROUND:Socioeconomically deprived children are at increased risk of ill-health associated with sedentary behavior, malnutrition, and helminth infection. The resulting reduced physical fitness, growth retardation, and impaired cognitive abilities may impede children's capacity to pay attention. The present study exa...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0005573

    authors: Gall S,Müller I,Walter C,Seelig H,Steenkamp L,Pühse U,du Randt R,Smith D,Adams L,Nqweniso S,Yap P,Ludyga S,Steinmann P,Utzinger J,Gerber M

    更新日期:2017-05-08 00:00:00

  • L-arginine availability and arginase activity: Characterization of amino acid permease 3 in Leishmania amazonensis.

    abstract:BACKGROUND:Leishmania uses the amino acid L-arginine as a substrate for arginase, enzyme that produces urea and ornithine, last precursor of polyamine pathway. This pathway is used by the parasite to replicate and it is essential to establish the infection in the mammalian host. L-arginine is not synthesized by the par...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0006025

    authors: Aoki JI,Muxel SM,Zampieri RA,Acuña SM,Fernandes JCR,Vanderlinde RH,Sales MCOP,Floeter-Winter LM

    更新日期:2017-10-26 00:00:00

  • STLV-1 co-infection is correlated with an increased SFV proviral load in the peripheral blood of SFV/STLV-1 naturally infected non-human primates.

    abstract::Simian T-Leukemia Virus type 1 and Simian Foamy Virus infect non-human primates. While STLV-1, as HTLV-1, causes Adult T-cell Leukemia/lymphoma, SFV infection is asymptomatic. Both retroviruses can be transmitted from NHPs to humans through bites that allow contact between infected saliva and recipient blood. Because ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0006812

    authors: Alais S,Pasquier A,Jegado B,Journo C,Rua R,Gessain A,Tobaly-Tapiero J,Lacoste R,Turpin J,Mahieux R

    更新日期:2018-10-01 00:00:00

  • Multiplex real-time PCR diagnostic of relapsing fevers in Africa.

    abstract:BACKGROUND:In Africa, relapsing fever borreliae are neglected arthropod-borne pathogens causing mild to deadly septicemia and miscarriage. The closely related Borrelia crocidurae, Borrelia duttonii, Borrelia recurrentis and Borrelia hispanica are rarely diagnosed at the species level, hampering refined epidemiological ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0002042

    authors: Elbir H,Henry M,Diatta G,Mediannikov O,Sokhna C,Tall A,Socolovschi C,Cutler SJ,Bilcha KD,Ali J,Campelo D,Barker SC,Raoult D,Drancourt M

    更新日期:2013-01-01 00:00:00

  • Cost-effectiveness of dog rabies vaccination programs in East Africa.

    abstract:BACKGROUND:Dog rabies annually causes 24,000-70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa. METHODS:RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0006490

    authors: Borse RH,Atkins CY,Gambhir M,Undurraga EA,Blanton JD,Kahn EB,Dyer JL,Rupprecht CE,Meltzer MI

    更新日期:2018-05-23 00:00:00

  • Unforeseen costs of cutting mosquito surveillance budgets.

    abstract::A budget proposal to stop the U.S. Centers for Disease Control and Prevention (CDC) funding in surveillance and research for mosquito-borne diseases such as dengue and West Nile virus has the potential to leave the country ill-prepared to handle new emerging diseases and manage existing ones. In order to demonstrate t...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000858

    authors: Vazquez-Prokopec GM,Chaves LF,Ritchie SA,Davis J,Kitron U

    更新日期:2010-10-26 00:00:00

  • Transcription Profiling of Malaria-Naïve and Semi-immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge.

    abstract:BACKGROUND:Continued exposure to malaria-causing parasites in endemic regions of malaria induces significant levels of acquired immunity in adult individuals. A better understanding of the transcriptional basis for this acquired immunological response may provide insight into how the immune system can be boosted during...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0003978

    authors: Rojas-Peña ML,Vallejo A,Herrera S,Gibson G,Arévalo-Herrera M

    更新日期:2015-08-05 00:00:00

  • Inferring the Spatio-temporal Patterns of Dengue Transmission from Surveillance Data in Guangzhou, China.

    abstract:BACKGROUND:Dengue is a serious vector-borne disease, and incidence rates have significantly increased during the past few years, particularly in 2014 in Guangzhou. The current situation is more complicated, due to various factors such as climate warming, urbanization, population increase, and human mobility. The purpos...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0004633

    authors: Zhu G,Liu J,Tan Q,Shi B

    更新日期:2016-04-22 00:00:00