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Toxoplasma gondii triggers release of human and mouse neutrophil extracellular traps

Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA.
Infection and immunity (Impact Factor: 4.16). 11/2011; 80(2):768-77. DOI: 10.1128/IAI.05730-11
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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.

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    • "NETs also modulate protozoan infections, trapping and killing Leishmania amazonensis promastigotes [18] while the promastigotes of Leishmania donovani are captured but not killed [19]. The protozoan parasite Toxoplasma gondii induces human and mouse neutrophils to release NETs that have microbicidal effects [20]. Yet, a role for NETs during parasitic helminth infections has not been described. "
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    • "Interestingly, in a presumably homogenous population of isolated neutrophils, only a small fraction of cells performs NETosis despite the fact that all cells are stimulated by the same trigger or touch the same stimulating pathogenic surface (Bruns et al, 2010). Thrown out NETs form a tight contact with pathogens as diverse as fungi (Fig 1) (Urban et al, 2006; Hasenberg et al, 2011b), bacteria (Beiter et al, 2006) and protozoa (Guimaraes-Costa et al, 2009; Abi Abdallah et al, 2012), during which many of the pathogens are also killed. However, as Mocsai (2013) recently pointed out, despite the massive response of the field towards this initial discovery and while the general concept of NETs as means to immobilize pathogens is now accepted, their role and importance in pathogen killing are still controversial (Menegazzi et al, 2012; Nauseef, 2012). "
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