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1.
PLoS Pathog ; 20(7): e1012349, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950076

RESUMO

Innate immune responses that allow hosts to survive infection depend on the action of multiple conserved signaling pathways. Pathogens and parasites in turn have evolved virulence factors to target these immune signaling pathways in an attempt to overcome host immunity. Consequently, the interactions between host immune molecules and pathogen virulence factors play an important role in determining the outcome of an infection. The immune responses of Drosophila melanogaster provide a valuable model to understand immune signaling and host-pathogen interactions. Flies are commonly infected by parasitoid wasps and mount a coordinated cellular immune response following infection. This response is characterized by the production of specialized blood cells called lamellocytes that form a tight capsule around wasp eggs in the host hemocoel. The conserved JAK-STAT signaling pathway has been implicated in lamellocyte proliferation and is required for successful encapsulation of wasp eggs. Here we show that activity of Stat92E, the D. melanogaster STAT ortholog, is induced in immune tissues following parasitoid infection. Virulent wasp species are able to suppress Stat92E activity during infection, suggesting they target JAK-STAT pathway activation as a virulence strategy. Furthermore, two wasp species (Leptopilina guineaensis and Ganaspis xanthopoda) suppress phenotypes associated with a gain-of-function mutation in hopscotch, the D. melanogaster JAK ortholog, indicating that they inhibit the activity of the core signaling components of the JAK-STAT pathway. Our data suggest that parasitoid wasp virulence factors block JAK-STAT signaling to overcome fly immune defenses.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Interações Hospedeiro-Parasita , Janus Quinases , Fatores de Transcrição STAT , Transdução de Sinais , Vespas , Animais , Drosophila melanogaster/parasitologia , Fatores de Transcrição STAT/metabolismo , Janus Quinases/metabolismo , Virulência , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Imunidade Inata
2.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34544850

RESUMO

In order to respond to infection, hosts must distinguish pathogens from their own tissues. This allows for the precise targeting of immune responses against pathogens and also ensures self-tolerance, the ability of the host to protect self tissues from immune damage. One way to maintain self-tolerance is to evolve a self signal and suppress any immune response directed at tissues that carry this signal. Here, we characterize the Drosophila tuSz1 mutant strain, which mounts an aberrant immune response against its own fat body. We demonstrate that this autoimmunity is the result of two mutations: 1) a mutation in the GCS1 gene that disrupts N-glycosylation of extracellular matrix proteins covering the fat body, and 2) a mutation in the Drosophila Janus Kinase ortholog that causes precocious activation of hemocytes. Our data indicate that N-glycans attached to extracellular matrix proteins serve as a self signal and that activated hemocytes attack tissues lacking this signal. The simplicity of this invertebrate self-recognition system and the ubiquity of its constituent parts suggests it may have functional homologs across animals.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/imunologia , Proteínas da Matriz Extracelular/metabolismo , Tolerância Imunológica/imunologia , Janus Quinases/metabolismo , Mutação , Tolerância a Antígenos Próprios , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Proteínas da Matriz Extracelular/genética , Glicosilação , Hemócitos , Janus Quinases/genética
3.
J Midwifery Womens Health ; 66(4): 512-519, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33661560

RESUMO

INTRODUCTION: Little is known about the nurse-midwifery workforce in rural Kansas hospitals, despite Kansas facing a shortage of primary care physicians providing maternity care rurally. This study investigated the current number of hospitals with certified nurse-midwives (CNMs) with privileges to attend births in Kansas hospitals located in frontier, rural, and densely settled rural counties and anticipated trends in the size of the CNM workforce at hospitals over the next 5 years. METHODS: Electronic surveys were distributed to senior hospital administrators at 94 hospitals in rural Kansas from June to July 2019. The survey included both open and closed-ended questions related to scope of CNM privileges, collaborative agreements, and forecasted trends in the CNM workforce in rural Kansas. RESULTS: Fifty-six hospitals completed the survey. Only one hospital reported having CNM-attended births. Twenty-eight of 37 hospital administrators agreed CNMs should have collaborative agreements with physicians. Most respondents did not anticipate the number of CNMs with privileges to increase at their hospitals over the next 5 years. DISCUSSION: Future research should focus on understanding the factors limiting CNM expansion in rural Kansas, because CNMs represent an untapped, additional maternity care workforce for rural Kansas.


Assuntos
Serviços de Saúde Materna , Tocologia , Enfermeiros Obstétricos , Feminino , Hospitais Rurais , Humanos , Kansas , Gravidez , Inquéritos e Questionários
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