CD40 in Endothelial Cells Restricts Neural Tissue Invasion by Toxoplasma gondii
| Autor: | Nicole L. Ward, Saad Saffo, George R. Dubyak, Myriam E. Rodriguez, Yalitza Lopez Corcino, Roxana E. Rojas, Barbara A. Fox, Zahra Toosi, Jose-Andres C. Portillo, Carlos S. Subauste, Jennifer Van Grol, David J. Bzik |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Immunology Microbiology Retina Mice 03 medical and health sciences 0302 clinical medicine Immune system Cell Movement Autophagy Leukocytes medicine Extracellular Animals HSP70 Heat-Shock Proteins CD40 Antigens Host Response and Inflammation CD40 biology Brain Endothelial Cells Toxoplasma gondii biology.organism_classification Cell biology Mice Inbred C57BL Endothelial stem cell 030104 developmental biology Infectious Diseases medicine.anatomical_structure 030220 oncology & carcinogenesis Humoral immunity biology.protein Parasitology Toxoplasma |
| Zdroj: | Infection and Immunity. 87 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00868-18 |
| Popis: | Little is known about whether pathogen invasion of neural tissue is affected by immune-based mechanisms in endothelial cells. We examined the effects of endothelial cell CD40 on Toxoplasma gondii invasion of the retina and brain, organs seeded hematogenously. T. gondii circulates in the bloodstream within infected leukocytes (including monocytes and dendritic cells) and as extracellular tachyzoites. After T. gondii infection, mice that expressed CD40 restricted to endothelial cells exhibited diminished parasite loads and histopathology in the retina and brain. These mice also had lower parasite loads in the retina and brain after intravenous (i.v.) injection of infected monocytes or dendritic cells. The protective effect of endothelial cell CD40 was not explained by changes in cellular or humoral immunity, reduced transmigration of leukocytes into neural tissue, or reduced invasion by extracellular parasites. Circulating T. gondii-infected leukocytes (dendritic cells used as a model) led to infection of neural endothelial cells. The number of foci of infection in these cells were reduced if endothelial cells expressed CD40. Infected dendritic cells and macrophages expressed membrane-associated inducible Hsp70. Infected leukocytes triggered Hsp70-dependent autophagy in CD40(+) endothelial cells and anti-T. gondii activity dependent on ULK1 and beclin 1. Reduced parasite load in the retina and brain not only required CD40 expression in endothelial cells but was also dependent on beclin 1 and the expression of inducible Hsp70 in dendritic cells. These studies suggest that during endothelial cell-leukocyte interaction, CD40 restricts T. gondii invasion of neural tissue through a mechanism that appears mediated by endothelial cell anti-parasitic activity stimulated by Hsp70. |
| Databáze: | OpenAIRE |
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