Toxoplasma gondii infection induces apoptosis in noninfected macrophages

Role of nitric oxide and other soluble factors

Y. Nishikawa, O. Kawase, O. Vielemeyer, H. Suzuki, Keith A Joiner, X. Xuan, H. Nagasawa

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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, NG-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.

Original languageEnglish (US)
Pages (from-to)375-385
Number of pages11
JournalParasite Immunology
Volume29
Issue number7
DOIs
StatePublished - Jul 2007

Fingerprint

Toxoplasmosis
Nitric Oxide
Macrophages
Apoptosis
Parasites
Toxoplasma
Nitric Oxide Synthase Type II
omega-N-Methylarginine
Parasitic Diseases
Infection
Nitric Oxide Synthase
Arginine
Acetates
Cell Line

Keywords

  • Apoptosis
  • IFN-γ
  • Nitric oxide
  • Toxoplasma gondii

ASJC Scopus subject areas

  • Parasitology
  • Immunology

Cite this

Toxoplasma gondii infection induces apoptosis in noninfected macrophages : Role of nitric oxide and other soluble factors. / Nishikawa, Y.; Kawase, O.; Vielemeyer, O.; Suzuki, H.; Joiner, Keith A; Xuan, X.; Nagasawa, H.

In: Parasite Immunology, Vol. 29, No. 7, 07.2007, p. 375-385.

Research output: Contribution to journalArticle

Nishikawa, Y. ; Kawase, O. ; Vielemeyer, O. ; Suzuki, H. ; Joiner, Keith A ; Xuan, X. ; Nagasawa, H. / Toxoplasma gondii infection induces apoptosis in noninfected macrophages : Role of nitric oxide and other soluble factors. In: Parasite Immunology. 2007 ; Vol. 29, No. 7. pp. 375-385.
@article{4b034cc1cc82489f86c1155e28c01dfd,
title = "Toxoplasma gondii infection induces apoptosis in noninfected macrophages: Role of nitric oxide and other soluble factors",
abstract = "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, NG-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",
author = "Y. Nishikawa and O. Kawase and O. Vielemeyer and H. Suzuki and Joiner, {Keith A} and X. Xuan and H. Nagasawa",
year = "2007",
month = "7",
doi = "10.1111/j.1365-3024.2007.00956.x",
language = "English (US)",
volume = "29",
pages = "375--385",
journal = "Parasite Immunology",
issn = "0141-9838",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Toxoplasma gondii infection induces apoptosis in noninfected macrophages

T2 - Role of nitric oxide and other soluble factors

AU - Nishikawa, Y.

AU - Kawase, O.

AU - Vielemeyer, O.

AU - Suzuki, H.

AU - Joiner, Keith A

AU - Xuan, X.

AU - Nagasawa, H.

PY - 2007/7

Y1 - 2007/7

N2 - 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, NG-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.

AB - 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, NG-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.

KW - Apoptosis

KW - IFN-γ

KW - Nitric oxide

KW - Toxoplasma gondii

UR - http://www.scopus.com/inward/record.url?scp=34250642807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250642807&partnerID=8YFLogxK

U2 - 10.1111/j.1365-3024.2007.00956.x

DO - 10.1111/j.1365-3024.2007.00956.x

M3 - Article

VL - 29

SP - 375

EP - 385

JO - Parasite Immunology

JF - Parasite Immunology

SN - 0141-9838

IS - 7

ER -