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Infection01:20

Infection

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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
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Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

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The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
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Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
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Pneumonia II: Pathophysiology01:29

Pneumonia II: Pathophysiology

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The pathophysiology of pneumonia involves the following steps:
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Stages of Infection01:26

Stages of Infection

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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
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Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Ciencia básica y patogénesis

Deniz Ghaffari1, Jennifer K Griffin1, Ye Zhou1

  • 1University of Toronto, Toronto, ON, Canada.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
PubMed
Resumen
Este resumen es generado por máquina.

La señalización de TREM2 de la microglía difiere entre cepas de ratones, lo que afecta la patología de la enfermedad de Alzheimer (EA). Los efectos de la deleción de ABI3 en modelos de EA pueden depender de estas variaciones en la vía TREM2.

Palabras clave:
microglíaTREM2enfermedad de AlzheimerABI3modelos de ratónseñalizaciónpatogénesisinmunologíaneurociencia

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Área de la Ciencia:

  • Neurociencia
  • Inmunología
  • Genética

Sus antecedentes:

  • La enfermedad de Alzheimer (EA) es una causa principal de demencia sin tratamientos eficaces.
  • La microglía, las células inmunitarias del cerebro, están implicadas en la patogénesis de la EA debido a variantes genéticas asociadas.
  • Existen resultados contradictorios sobre el papel de la deleción de ABI3 en modelos de ratón de EA, lo que sugiere diferencias biológicas subyacentes.

Objetivo del estudio:

  • Investigar el impacto de las diferencias en el fondo genético en la señalización de TREM2 en la microglía.
  • Explorar cómo la señalización alterada de TREM2 en diferentes poblaciones de microglía puede explicar las discrepancias en los estudios de deleción de ABI3 para la EA.
  • Identificar posibles dianas terapéuticas mediante la comprensión de la interacción entre TREM2 y ABI3 en la EA.

Principales métodos:

  • Se utilizaron microglías primarias de ratones C57 y SJL.
  • La escisión de TREM2 se midió mediante ELISA.
  • Los componentes de la vía de señalización de TREM2 (SYK, PLCG2) se analizaron mediante western blot después de la estimulación con anticuerpos anti-TREM2.
  • La fagocitosis de beta amiloide por la microglía se evaluó mediante imágenes en vivo.

Principales resultados:

  • La microglía SJL exhibió una escisión de TREM2 significativamente menor en comparación con la microglía C57.
  • La estimulación de la microglía SJL con un anticuerpo anti-TREM2 resultó en una fosforilación atenuada de SYK y PLCG2.
  • La microglía SJL mostró una fagocitosis reducida de beta amiloide en comparación con la microglía C57, lo que indica una función alterada de TREM2.

Conclusiones:

  • La señalización de TREM2 y las funciones relacionadas con la EA se alteran significativamente en la microglía SJL.
  • Las diferencias en la señalización de TREM2 entre las poblaciones de microglía pueden explicar los fenotipos contradictorios de la EA observados en los modelos de ratón deficientes en ABI3.
  • Investigaciones adicionales tienen como objetivo dilucidar el vínculo molecular entre TREM2 y ABI3 para desarrollar nuevos productos terapéuticos para la EA.