Infect Immun. 2013 Mar 18. [Epub ahead of print]
CD40 induces anti-Toxoplasma gondii activity in non-hematopoietic cells dependent on autophagy proteins
Van Grol J, Muniz-Feliciano L, Portillo JA, Bonilha VL, Subauste CS
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106
Toxoplasma gondii infects both hematopoietic and non-hematopoietic cells and can cause cerebral and ocular toxoplasmosis, either as a result of congenital or post-natally acquired infections. Host protection likely acts at both cellular levels to control the parasite. CD40 is key for protection against cerebral and ocular toxoplasmosis. We determined if CD40 induces anti-T. gondii activity at the level of non-hematopoietic cells. Engagement of CD40 on various endothelial cells including human microvascular brain endothelial cells, human umbilical vein endothelial cells, 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 non-hematopoietic cells dependent on proteins of the autophagy machinery.
PMID: 23509150 [PubMed - as supplied by publisher]