In situ inflammasome activation results in severe damage to the central nervous system in fatal Zika virus microcephaly cases

Autor: Barbara Cristina Baldez Vasconcelos, Beatriz H. Baldez Vasconcelos, Arnaldo Jorge Martins Filho, Marialva Tereza Ferreira de Araújo, Ana Cecília Ribeiro Cruz, Lívia Carício Martins, Pedro Fernando da Costa Vasconcelos, Jannifer Oliveira Chiang, Consuelo Silva de Oliveira, Ermelinda do Rosário Moutinho da Cruz, Raimunda do Socorro da Silva Azevedo, Jorge Rodrigues de Sousa, Livia Medeiros Neves Casseb, Juarez Antônio Simões Quaresma
Rok vydání: 2018
Předmět:
0301 basic medicine
Central Nervous System
Male
Microcephaly
Pathology
Inflammasomes
Biochemistry
Infec??es por Flavivirus
Piroptose / gen?tica
Zika virus
Complexos Multiproteicos
Pregnancy
Immunology and Allergy
Pregnancy Complications
Infectious
biology
Zika Virus Infection
Infec??o pelo Zika virus / patologia
Pyroptosis
virus diseases
Brain
Inflammasome
Hematology
Cytokines
Female
medicine.symptom
medicine.drug
medicine.medical_specialty
C?rtex Cerebral / les?es
Apoptose / gen?tica
Immunology
Caspase 1
Sistema Nervoso Central / anormalidades
Microcefalia / mortalidade
03 medical and health sciences
AIM2
Fetus
medicine
Humans
Molecular Biology
Inflamassomos / gen?tica
business.industry
Infant
Newborn
Zika Virus
biology.organism_classification
medicine.disease
Zika virus / patogenicidade
Mononuclear cell infiltration
030104 developmental biology
Gliosis
business
Zdroj: Repositório Digital do Instituto Evandro Chagas (Patuá)
Instituto Evandro Chagas (IEC)
instacron:IEC
ISSN: 1096-0023
Popis: Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Federal University of Par?. Tropical Medicine Center. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil / Federal University of Par?. Tropical Medicine Center. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. Zika virus (ZIKV) has caused substantial concern worldwide owing to its association with severe birth defects, such as microcephaly and other congenital malformations. Inflammasomes, i.e., multi-protein complexes that induce inflammation and pyroptosis, are predicted to contribute to the immune response to this flavivirus. Accordingly, in this study, the in situ inflammasome response was evaluated in fatal cases of ZIKV-linked microcephaly. Brain tissue samples were collected from eight babies, including four ZIKV-positive microcephalic neonates who died after birth and four flavivirus-negative neonatal controls who died of other causes and whose central nervous system (CNS) architecture was preserved. In the ZIKV-positive newborn/stillbirth babies, the major histopathological alterations included atrophy of the cortical layer, a predominance of mononuclear cell infiltration in the Virchow-Robin space, neuronal necrosis, vacuolization and neuronal degeneration, neuronophagy, and gliosis. An immunohistochemical analysis of tissues in the neural parenchyma showed significantly higher expression of the receptors NLRP1, NLRP3, and AIM2, cytokines IL-1?, IL-18, and IL-33, and enzymes caspase 1, iNOS, and arginase 1 in ZIKV-positive microcephaly cases than in flavivirus-negative controls. These results suggest that inflammasome activation can aggravate the neuroinflammatory response and consequently increase CNS damage in neonates with fetal neural ZIKV infection and microcephaly.
Databáze: OpenAIRE
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