Induction of Nitric Oxide Synthase Protects Against Malaria in Mice Exposed to Irradiated Plasmodium Berghei Infected Mosquitoes: Involvement of Interferon Gamma and CD8+ T Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1994 Jul 1

PMID 7516412

Citations 77

Authors

M C Seguin

F W Klotz

I Schneider

J P Weir

M Goodbary

M Slayter

J J Raney

J U Aniagolu

S J Green

Affiliations

Soon will be listed here.

Abstract

Exposure of BALB/c mice to mosquitoes infected with irradiated Plasmodium berghei confers protective immunity against subsequent sporozoite challenge. Immunized mice challenged with viable sporozoites develop parasitemia when treated orally with substrate inhibitors of nitric oxide synthase (NOS). This suggests that the production of nitric oxide (NO) prevents the development of exoerythrocytic stages of malaria in liver. Liver tissue from immunized mice expressed maximal levels of mRNA for inducible NOS (iNOS) between 12 and 24 h after challenge with sporozoites. Intraperitoneal injection of neutralizing monoclonal antibody against interferon gamma (IFN-gamma) or in vivo depletion of CD8+ T cells, but not CD4+ T cells, at the time of challenge blocked expression of iNOS mRNA and ablated protection in immunized mice. These results show that both CD8+ T cells and IFN-gamma are important components in the regulation of iNOS in liver which contributes to the protective response of mice immunized with irradiated malaria sporozoites. IFN-gamma, likely provided by malaria-specific CD8+ T cells, induces liver cells, hepatocytes and/or Kupffer cells, to produce NO for the destruction of infected hepatocytes or the parasite within these cells.

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References

Nussenzweig R, Vanderberg J, MOST H, Orton C . Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. Nature. 1967; 216(5111):160-2. DOI: 10.1038/216160a0. View

Geller D, Di Silvio M, Nussler A, Wang S, Shapiro R, Simmons R . Nitric oxide synthase expression is induced in hepatocytes in vivo during hepatic inflammation. J Surg Res. 1993; 55(4):427-32. DOI: 10.1006/jsre.1993.1164. View

Ferreira A, Schofield L, Enea V, Schellekens H, van der Meide P, Collins W . Inhibition of development of exoerythrocytic forms of malaria parasites by gamma-interferon. Science. 1986; 232(4752):881-4. DOI: 10.1126/science.3085218. View

Weiss W, Sedegah M, Beaudoin R, MILLER L, Good M . CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proc Natl Acad Sci U S A. 1988; 85(2):573-6. PMC: 279593. DOI: 10.1073/pnas.85.2.573. View

Romero P, Maryanski J, Corradin G, Nussenzweig R, NUSSENZWEIG V, Zavala F . Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989; 341(6240):323-6. DOI: 10.1038/341323a0. View

Weiss W, Good M, Hollingdale M, MILLER L, Berzofsky J . Genetic control of immunity to Plasmodium yoelii sporozoites. J Immunol. 1989; 143(12):4263-6. View

Weiss W, Mellouk S, Houghten R, Sedegah M, Kumar S, Good M . Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes. J Exp Med. 1990; 171(3):763-73. PMC: 2187765. DOI: 10.1084/jem.171.3.763. View

Aggarwal A, Kumar S, Jaffe R, Hone D, Gross M, Sadoff J . Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells. J Exp Med. 1990; 172(4):1083-90. PMC: 2188594. DOI: 10.1084/jem.172.4.1083. View

Nussler A, Drapier J, Renia L, Pied S, Miltgen F, Gentilini M . L-arginine-dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation. Eur J Immunol. 1991; 21(1):227-30. DOI: 10.1002/eji.1830210134. View

10.

Mellouk S, Green S, Nacy C, Hoffman S . IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol. 1991; 146(11):3971-6. View

11.

Rodrigues M, Cordey A, Arreaza G, Corradin G, Romero P, Maryanski J . CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria. Int Immunol. 1991; 3(6):579-85. DOI: 10.1093/intimm/3.6.579. View

12.

Lyons C, Orloff G, Cunningham J . Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. J Biol Chem. 1992; 267(9):6370-4. View

13.

Xie Q, Cho H, Calaycay J, Mumford R, Swiderek K, Lee T . Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science. 1992; 256(5054):225-8. DOI: 10.1126/science.1373522. View

14.

Corbett J, Tilton R, Chang K, Hasan K, Ido Y, Wang J . Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes. 1992; 41(4):552-6. DOI: 10.2337/diab.41.4.552. View

15.

Nussler A, Di Silvio M, Billiar T, Hoffman R, Geller D, Selby R . Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J Exp Med. 1992; 176(1):261-4. PMC: 2119287. DOI: 10.1084/jem.176.1.261. View

16.

Nussler A, Renia L, Pasquetto V, Miltgen F, Matile H, Mazier D . In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants. Eur J Immunol. 1993; 23(4):882-7. DOI: 10.1002/eji.1830230417. View

17.

Taylor-Robinson A, Phillips R, Severn A, Moncada S, Liew F . The role of TH1 and TH2 cells in a rodent malaria infection. Science. 1993; 260(5116):1931-4. DOI: 10.1126/science.8100366. View

18.

Weiss W, Sedegah M, Berzofsky J, Hoffman S . The role of CD4+ T cells in immunity to malaria sporozoites. J Immunol. 1993; 151(5):2690-8. View

19.

Schreiber R, Hicks L, Celada A, Buchmeier N, Gray P . Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity. J Immunol. 1985; 134(3):1609-18. View