CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins

Toxoplasma gondii infects both hematopoietic and nonhematopoietic cells and can cause cerebral and ocular toxoplasmosis, as a result of either congenital or postnatally acquired infections. Host protection likely acts at both cellular levels to control the parasite. CD40 is a key factor for protecti...

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Format: Article
Language:en
Published: American Society for Microbiology 2013
Subjects:
Fungal and Parasitic Infections
Online Access:https://ncbi.nlm.nih.gov/pmc/articles/PMC3676008/
https://ncbi.nlm.nih.gov/pubmed/23509150
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/IAI.01145-12
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id pubmed-3676008
record_format dspace
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Fungal and Parasitic Infections
spellingShingle Fungal and Parasitic Infections
CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins
topic_facet Fungal and Parasitic Infections
description Toxoplasma gondii infects both hematopoietic and nonhematopoietic cells and can cause cerebral and ocular toxoplasmosis, as a result of either congenital or postnatally acquired infections. Host protection likely acts at both cellular levels to control the parasite. CD40 is a key factor for protection against cerebral and ocular toxoplasmosis. We determined if CD40 induces anti-T. gondii activity at the level of nonhematopoietic cells. Engagement of CD40 on various endothelial cells including human microvascular brain endothelial cells, human umbilical vein endothelial cells, and a mouse endothelial cell line as well as human and mouse retinal pigment epithelial cells resulted in killing of T. gondii. CD40 stimulation increased expression of the autophagy proteins Beclin 1 and LC3 II, enhanced autophagy flux, and led to recruitment of LC3 around the parasite. The late endosomal/lysosomal marker LAMP-1 accumulated around the parasite in CD40-stimulated cells. This was accompanied by killing of T. gondii dependent on lysosomal enzymes. Accumulation of LAMP-1 and killing of T. gondii were dependent on the autophagy proteins Beclin 1 and Atg7. Together, these studies revealed that CD40 induces toxoplasmacidal activity in various nonhematopoietic cells dependent on proteins of the autophagy machinery.
author_sort Van Grol, Jennifer
title CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins
title_short CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins
title_full CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins
title_fullStr CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins
title_full_unstemmed CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins
title_sort cd40 induces anti-toxoplasma gondii activity in nonhematopoietic cells dependent on autophagy proteins
publisher American Society for Microbiology
publisher_facet American Society for Microbiology
publishDate 2013
url https://ncbi.nlm.nih.gov/pmc/articles/PMC3676008/
https://ncbi.nlm.nih.gov/pubmed/23509150
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/IAI.01145-12
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