Toxoplasma gondii infection induces apoptosis in noninfected macrophages: role of nitric oxide and other soluble factors

Authors: NISHIKAWA, Y.¹; KAWASE, O.¹; VIELEMEYER, O.²; SUZUKI, H.¹; JOINER, K. A.³; XUAN, X.¹; NAGASAWA, H.¹

Source: Parasite Immunology, Volume 29, Number 7, July 2007 , pp. 375-385(11)

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Abstract:

SUMMARY

Apoptosis has been found to help in the defence against pathogens. Infection with the obligate intracellular parasite Toxoplasma gondii is known to trigger host-cell apoptosis. When using a T. gondii-infected macrophage cell line, J774A.1, treatment with IFN-γ significantly enhanced apoptosis in noninfected bystander cells while parasitized cells became relatively resistant. Infection and IFN-γ treatment activated the expression of inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO) and treatment of cells with an iNOS inhibitor, N^G-monomethlyl-l-arginine acetate (l-NMMA) reduced the apoptosis frequency. However, the reversal was only partial suggesting that not only NO, but also other, as of yet, unknown factors are induced. Finally, we studied the effect in vivo by infecting mice with either a virulent or an avirulent strain. Challenge with the virulent strain lead to a higher parasite burden, induced host-cell apoptosis in peritoneal cells, and produced higher levels of IFN-γ and NO. Moreover, treatment of mice with a NO synthase inhibitor, aminoguanidine, partially inhibited the host-cell apoptosis induced by the parasite infection. Altogether, our findings indicate that apoptosis in bystander host cells is due to the secretion of NO and other soluble factors released by parasite-infected cells.

Keywords: apoptosis; IFN-γ; nitric oxide; Toxoplasma gondii

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-3024.2007.00956.x

Affiliations: 1: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan, 2: Laboratoires Constant Burg, Institut Curie, Paris, France, 3: Arizona Health Science Center, University of Arizona, College of Medicine, Tucson, AZ, USA

Publication date: 2007-07-01

Toxoplasma gondii infection induces apoptosis in noninfected macrophages: role of nitric oxide and other soluble factors

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