Stimulation of nitric oxide production in macrophages by Babesia bovis.

Gamma interferon (IFN-gamma)-activated macrophages are believed to play a key role in resistance to Babesia bovis through parasite suppression by macrophage secretory products. However, relatively little is known about interactions between this intraerythrocytic parasite and the macrophages of its bovine host. In this study, we examined the in vitro effect of intact and fractionated B. bovis merozoites on bovine macrophage nitric oxide (NO) production. In the presence of IFN-gamma, B. bovis merozoites stimulated NO production, as indicated by the presence of increased L-arginine-dependent nitrite (NO2-) levels in culture supernatants of macrophages isolated from several cattle. The merozoite crude membrane (CM) fraction stimulated greater production of NO, in a dose-dependent manner, than did the merozoite homogenate or the soluble, cytosolic high-speed supernatant fraction. Stimulation of NO production by CM was enhanced by as little as 1 U of IFN-gamma per ml of culture medium. Upregulation of inducible NO synthase mRNA in bovine macrophages by either B. bovis-parasitized erythrocytes and IFN-gamma or CM was also observed. B. bovis-specific T-helper lymphocyte culture supernatants, all of which contained IFN-gamma, were also found to induce L-arginine-dependent NO2- production. Supernatants that induced the highest levels of NO also contained biologically active TNF. These results show that B. bovis merozoites and antigen-stimulated B. bovis-immune T cells can induce the production of NO, a molecule implicated in both protection and pathologic changes associated with hemoprotozoan parasite infections.

[1]  W. Brown,et al.  Cloning and expression of caprine interferon-gamma. , 1998, Gene.

[2]  P. Arese,et al.  Mycoplasma contamination of Plasmodium cultures--a case of parasite parasitism. , 1997, Parasitology today.

[3]  A. Taylor-Robinson.  Antimalarial activity of nitric oxide: cytostasis and cytotoxicity towards Plasmodium falciparum. , 1997, Biochemical Society transactions.

[4]  M. Good,et al.  Prolonged Th1‐like response generated by a Plasmodium yoeli‐specific T cell clone allows complete clearance of infection in reconstituted mice , 1997, Parasite immunology.

[5]  M. Rafie-Kolpin,et al.  Identification and comparison of macrophage-induced proteins and proteins induced under various stress conditions in Brucella abortus , 1996, Infection and immunity.

[6]  C. Cluff,et al.  Assessment of bovine mononuclear phagocytes and neutrophils for induced L-arginine-dependent nitric oxide production. , 1996, Veterinary immunology and immunopathology.

[7]  C. Griot,et al.  Differential and strain-specific triggering of bovine alveolar macrophage effector functions by mycoplasmas. , 1996, Microbial pathogenesis.

[8]  H. Kolb,et al.  Interleukin-12 gene-expression of macrophages is regulated by nitric oxide. , 1996, Biochemical and biophysical research communications.

[9]  C. Cluff,et al.  Reactive Oxygen and Nitrogen Intermediates and Products from Polyamine Degradation Are Babesiacidal In Vitro a , 1996, Annals of the New York Academy of Sciences.

[10]  D. Kwiatkowski,et al.  In vitro induction of nitric oxide by an extract of Plasmodium falciparum. , 1996, The Journal of infection.

[11]  D. Radzioch,et al.  A Th1-associated increase in tumor necrosis factor alpha expression in the spleen correlates with resistance to blood-stage malaria in mice , 1996, Infection and immunity.

[12]  D. Beezhold,et al.  Mycoplasma hyorhinis molecules that induce tumor necrosis factor alpha secretion by human monocytes , 1995, Infection and immunity.

[13]  I. Charles,et al.  Altered immune responses in mice lacking inducible nitric oxide synthase , 1995, Nature.

[14]  E. Peterhans,et al.  Inducible nitric oxide synthase in cattle. Differential cytokine regulation of nitric oxide synthase in bovine and murine macrophages. , 1995, Journal of immunology.

[15]  W. Brown,et al.  Identification of candidate vaccine antigens of bovine hemoparasites Theileria parva and Babesia bovis by use of helper T cell clones. , 1995, Veterinary parasitology.

[16]  D. Carvajal,et al.  Mouse interleukin‐12 (IL‐12) p40 homodimer: a potent IL‐12 antagonist , 1995, European journal of immunology.

[17]  J. Currier,et al.  Inhibition of Plasmodium falciparum growth in vitro by CD4+ and CD8+ T cells from non‐exposed donors , 1994, Parasite immunology.

[18]  C. Chitko-McKown,et al.  Interleukin-10 is expressed by bovine type 1 helper, type 2 helper, and unrestricted parasite-specific T-cell clones and inhibits proliferation of all three subsets in an accessory-cell-dependent manner , 1994, Infection and immunity.

[19]  J. Berzofsky,et al.  Analysis of human T cell clones specific for conserved peptide sequences within malaria proteins. Paucity of clones responsive to intact parasites. , 1994, Journal of immunology.

[20]  E. Peterhans,et al.  Noncytopathic strains of bovine viral diarrhea virus prime bovine bone marrow-derived macrophages for enhanced generation of nitric oxide. , 1994, Biochemical and biophysical research communications.

[21]  P. Perlmann,et al.  Human monocytes cultured with and without interferon‐gamma inhibit Plasmodium falciparum parasite growth in vitro via secretion of reactive nitrogen intermediates , 1994, Parasite immunology.

[22]  D. Dobbelaere,et al.  Heterogeneity in cytokine profiles of Babesia bovis-specific bovine CD4+ T cells clones activated in vitro , 1993, Infection and immunity.

[23]  S. Moncada,et al.  The role of TH1 and TH2 cells in a rodent malaria infection. , 1993, Science.

[24]  P. Kremsner,et al.  Malaria antigen and cytokine-induced production of reactive nitrogen intermediates by murine macrophages: no relevance to the development of experimental cerebral malaria. , 1993, Immunology.

[25]  W. Brown,et al.  Bovine helper T cell clones recognize five distinct epitopes on Babesia bovis merozoite antigens , 1992, Infection and immunity.

[26]  B. Aggarwal,et al.  In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: possible roles in malaria , 1992, Infection and immunity.

[27]  R. M. McLaughlin,et al.  The effect of neutrophils, tumor necrosis factor, and granulocyte macrophage/colony stimulating factor on Babesia bovis and Babesia bigemina in culture. , 1992, Veterinary parasitology.

[28]  A. Ferrante,et al.  IL-4 inhibits macrophage-mediated killing of Plasmodium falciparum in vitro. A possible parasite-immune evasion mechanism. , 1992, Journal of immunology.

[29]  N. Yamaguchi,et al.  Induction of Cytokines in Human Peripheral Blood Mononuclear Cells by Mycoplasmas , 1992, Microbiology and immunology.

[30]  W. Brown,et al.  Babesia bovis: bovine helper T cell lines reactive with soluble and membrane antigens of merozoites. , 1992, Experimental parasitology.

[31]  K. Rockett,et al.  Killing of Plasmodium falciparum in vitro by nitric oxide derivatives , 1991, Infection and immunity.

[32]  W. Brown,et al.  Cell-mediated immune responses to Babesia bovis merozoite antigens in cattle following infection with tick-derived or cultured parasites , 1991, Infection and immunity.

[33]  D. Kwiatkowski,et al.  Two soluble antigens of Plasmodium falciparum induce tumor necrosis factor release from macrophages , 1990, Infection and immunity.

[34]  J. Playfair,et al.  Malaria exoantigens induce TNF, are toxic and are blocked by T-independent antibody. , 1990, Immunology letters.

[35]  S. Hoffman,et al.  Cellular mechanisms of nonspecific immunity to intracellular infection: cytokine-induced synthesis of toxic nitrogen oxides from L-arginine by macrophages and hepatocytes. , 1990, Immunology letters.

[36]  L. Miller,et al.  Cellular mechanisms in immunity to blood stage infection. , 1990, Immunology letters.

[37]  J. Playfair,et al.  Human and murine macrophages produce TNF in response to soluble antigens of Plasmodium falciparum , 1990, Parasite immunology.

[38]  M. Meltzer,et al.  Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. , 1990, Journal of immunology.

[39]  P. Ambroise‐Thomas,et al.  Tumor necrosis factor production by human macrophages stimulated in vitro by Plasmodium falciparum , 1990, Infection and immunity.

[40]  P. Vassalli,et al.  Tumor‐Necrosis Factor and other Cytokines in Cerebral Malaria: Experimental and Clinical Data , 1989, Immunological reviews.

[41]  J. Playfair,et al.  Soluble malarial antigens are toxic and induce the production of tumour necrosis factor in vivo. , 1989, Immunology.

[42]  I. Clark,et al.  Immunopathophysiology of Babesia bovis and Plasmodium falciparum infections. , 1988, Parasitology today.

[43]  J. Playfair,et al.  Malarial parasites induce TNF production by macrophages. , 1988, Immunology.

[44]  I. Clark,et al.  Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-gamma or tumor necrosis factor, and its enhancement by butylated hydroxyanisole. , 1987, Journal of immunology.

[45]  M. Levy,et al.  Growth inhibition of Babesia bovis in culture by secretions from bovine mononuclear phagocytes , 1985, Infection and immunity.

[46]  H. Shear,et al.  Induction of crisis forms in the human malaria parasite Plasmodium falciparum by gamma-interferon-activated, monocyte-derived macrophages. , 1984, Journal of immunology.

[47]  D. Morris,et al.  Regulation of protein synthesis in mitogen-activated bovine lymphocytes. Analysis of actin-specific and total mRNA accumulation and utilization. , 1983, The Journal of biological chemistry.

[48]  W. Hanson,et al.  Transfer of immunity to Babesia microti of human origin using T lymphocytes in mice. , 1980, Cellular immunology.

[49]  R. H. Jacobson,et al.  Babesia bovis: In vitro phagocytosis promoted by immune serum and by antibodies produced against protective antigens , 2004, Parasitology Research.

[50]  W. Brown,et al.  Babesia bovis: common protein fractions recognized by oligoclonal B. bovis-specific CD4+ T cell lines from genetically diverse cattle. , 1999, Experimental parasitology.

[51]  G. Trinchieri.  Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. , 1995, Annual review of immunology.

[52]  G. K. Allen,et al.  IFN-gamma stimulates IgG2 production from bovine B cells costimulated with anti-mu and mitogen. , 1994, Cellular immunology.

[53]  W. Brown,et al.  Use of helper T cells to identify potential vaccine antigens of Babesia bovis. , 1994, Parasitology today.

[54]  M. Tam,et al.  Role of interferon-gamma and tumor necrosis factor in host resistance to Plasmodium chabaudi AS. , 1990, Immunology letters.