Toxoplasma gondii Triggers Release of Human and Mouse Neutrophil Extracellular Traps Delbert S. Abi Abdallah a , Changyou Lin b , Carissa J. Ball c , Michael R. King c , Gerald E. Duhamel b and Eric Y. Denkers a a Department of Microbiology and Immunology b Department of Biomedical Sciences c College of Veterinary Medicine, Department of Biomedical Engineering, College of Engineering, Cornell University, Ithaca, New York, USA J. H. Adams , Editor ABSTRACT Neutrophils have recently been shown to release DNA-based extracellular traps that contribute to microbicidal killing and have also been implicated in autoimmunity. The role of neutrophil extracellular trap (NET) formation in the host response to nonbacterial pathogens has received much less attention. Here, we show that the protozoan pathogen Toxoplasma gondii elicits the production of NETs from human and mouse neutrophils. Tachyzoites of each of the three major parasite strain types were efficiently entrapped within NETs, resulting in decreased parasite viability. We also show that Toxoplasma activates a MEK-extracellular signal-regulated kinase (ERK) pathway in neutrophils and that the inhibition of this pathway leads to decreased NET formation. To determine if Toxoplasma induced NET formation in vivo , we employed a mouse intranasal infection model. We found that the administration of tachyzoites by this route induced a rapid tissue recruitment of neutrophils with evidence of extracellular DNA release. Taken together, these data indicate a role for NETs in the host innate response to protozoan infection. We propose that NET formation limits infection by direct microbicidal effects on Toxoplasma as well as by interfering with the ability of the parasite to invade target host cells.
Toxoplasma gondii Triggers Release of Human and Mouse Neutrophil Extracellular Traps
Abstract
Toxoplasma gondii Triggers Release of Human and Mouse Neutrophil Extracellular Traps Delbert S. Abi Abdallah a , Changyou Lin b , Carissa J. Ball c , Michael R. King c , Gerald E. Duhamel b and Eric Y. Denkers a a Department of Microbiology and Immunology b Department of Biomedical Sciences c College of Veterinary Medicine, Department of Biomedical Engineering, College of Engineering, Cornell University, Ithaca, New York, USA J. H. Adams , Editor ABSTRACT Neutrophils have recently been shown to release DNA-based extracellular traps that contribute to microbicidal killing and have also been implicated in autoimmunity. The role of neutrophil extracellular trap (NET) formation in the host response to nonbacterial pathogens has received much less attention. Here, we show that the protozoan pathogen Toxoplasma gondii elicits the production of NETs from human and mouse neutrophils. Tachyzoites of each of the three major parasite strain types were efficiently entrapped within NETs, resulting in decreased parasite viability. We also show that Toxoplasma activates a MEK-extracellular signal-regulated kinase (ERK) pathway in neutrophils and that the inhibition of this pathway leads to decreased NET formation. To determine if Toxoplasma induced NET formation in vivo , we employed a mouse intranasal infection model. We found that the administration of tachyzoites by this route induced a rapid tissue recruitment of neutrophils with evidence of extracellular DNA release. Taken together, these data indicate a role for NETs in the host innate response to protozoan infection. We propose that NET formation limits infection by direct microbicidal effects on Toxoplasma as well as by interfering with the ability of the parasite to invade target host cells.Preview Only. This article cannot be rented because we do not currently have permission from the publisher.
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Toxoplasma gondii Triggers Release of Human and Mouse Neutrophil Extracellular Traps
Abi Abdallah, Delbert S.; Lin, Changyou; Ball, Carissa J.; King, Michael R.; Duhamel, Gerald E.; Denkers, Eric Y.
Follow Infection and Immunity
, Volume 80 (2): 768
American Society For Microbiology – Feb 1, 2012
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