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Trypanosomes, T cells and transgenic mice
News & Comment
include treatment, trypanotolerance, drugs and drug resistance. Field operations are PATTEC’s main concern. There is a shared membership and joint meetings will be encouraged. JT
Trypanosomes, T cells and transgenic mice
TRENDS in Parasitology Vol.17 No.7 July 2001
results stress the need for quality control programmes to ensure accurate diagnosis of parasitic infections. Some countries run such programmes at national levels to train laboratories. With globalization of our society, a more centralized approach is necessary. Initiatives like that of the FAO are a major step towards achieving this goal. TS
Protozoal DNA triggers innate immunity
A new study in genetically modified ‘transgenic’ mice provides strong evidence that antigen-specific T helper type 1 (Th1) but not Th2 cells protect mice from lethal infection with Trypanosoma cruzi. S. Kumar and R. Tarleton [(2001) J. Immunol. 166, 4596–4603] found that transfer of Th1 cells to mice before their infection with trypanosomes could dramatically lower parasitemia and increase survival compared to mice that received no cells. By contrast, transfer of Th2 cells resulted in higher parasite levels, greater tissue inflammation and increased mortality. The use of the transgenic mice in combination with specially modified parasites was crucial for this study, because it confirmed the specificity of the T cells for the parasites. SHK
Preference for a reference Diagnosis of parasitic infection is an important aid in the control of infection. However, there is little or no harmonization between different laboratories over which techniques are used to detect infections, making comparison of data difficult. Recently, the use of enzyme-linked immunosorbent assays (ELISA) methods to detect antibodies against trypanosomes was evaluated by the FAO [Rebeski, D. et al. (2001) Vet. Parasitol. 96, 11–50]. Microtitre ELISA plates that were precoated with antigen were shipped to 15 diagnostic laboratories in Africa and Europe. Internal quality control samples were also provided. A detailed analysis of the results obtained in different laboratories allowed the source of errors in the operational performance of the tests to be detected. The
The recognition of protozoal DNA by immune cells could provide an important innate defense mechanism for control of parasitic disease. By culturing macrophages with DNA from Babesia bovis, Trypanosoma cruzi and T. brucei, L. Shoda et al. [(2001) Infect. Immun. 69, 2162–2171] found increased production of pro-inflammatory cytokines IL-12 and TNF-α, in addition to enhanced nitric oxide synthesis. In particular, unmethylated CpG dinucleotides were found to induce strongly macrophage production of these mediators, all three of which are associated with protective immunity against protozoan parasites. Protozoan DNA also has a strong mitogenic effect on B lymphocytes. SHK
311
immunity when formulated with a sugar cube, which is subsequently swallowed. In some cases, to induce protection at the mucosal interface between host and environment, the actual site of vaccine administration is not crucial. Immunity to pathogens that inhabit the intestinal tract can be induced by administration of the vaccine at other mucosal surfaces, such as the mucosae of the nose. However, as with most non-infective vaccines, an adjuvant is required to trigger strong protective responses. Cholera toxin and enterotoxin (LT) are powerful mucosal adjuvants but they are not permitted for human use because of their toxic properties. Recently, non-toxic mutants of LT have been produced and tested for their immunopotentiating effect when combined with a surface antigen of Toxoplasma gondii [SAG1; Bonenfant, C. et al. (2001) Infect. Immun. 69, 1605–1612]. The vaccine preparations were administered intranasally in mice. High-level protection was observed after virulent challenge infection with infectious T. gondii cysts. TS
Trypanosoma brucei’s heel?
Nothing to spit at The identification of an immunosuppressive protein in the saliva of ticks may help explain the pathogenicity of Lyme disease and other tick-borne illnesses. The protein was recently identified in saliva of the hard tick Ixodes scapularis by R. Gillespie et al. [(2001) J. Immunol. 166, 4319–4326]. It has been tagged an ‘interleukin-2 (IL-2) binding factor’ because of its ability to prevent the action of IL-2. A member of the IL family of cytokines, IL-2 normally induces T-cell proliferation and leukocyte activation during the generation of immune responses. By preventing these processes, the IL-2 binding factor effectively increases the survival and infectivity of pathogens introduced with tick saliva. The binding factor is specific for both mouse and human IL-2. SHK
The smell of a Toxoplasma vaccine Non-invasive administration of vaccines is preferred over invasive methods, such as injection. Depending on the type of immune reactivity that is required alternative methods might be applicable. The poliomyelitis vaccine is known for its potential to induce
African sleeping sickness caused by Trypanosoma brucei has devastating effects on the cattle population in Africa. The development of vaccines is hampered by the fact that these parasites have developed a highly efficient system to change their phenotypical appearance known as antigenic variation. The outcome of an infection appears to be the result of the balance between the parasite varying the molecules that constitute the surface coat, and the immune system generating specific antibodies against each variant surface molecule. Apart from vector control, the use of therapeutics is necessary. Researchers have now identified a new enzyme that is crucial for the survival of the parasite [Schnaufer et al. (2001) Science 291, 2159–2162]. The enzyme plays a key role in the RNA-editing process required to obtain mature mitochondrial RNA. Repression of the activity of the enzyme resulted in death of early-stage parasites. The results suggest that
http://parasites.trends.com 1471-4922/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
include treatment, trypanotolerance, drugs and drug resistance. Field operations are PATTEC’s main concern. There is a shared membership and joint meetings will be encouraged. JT
Trypanosomes, T cells and transgenic mice
TRENDS in Parasitology Vol.17 No.7 July 2001
results stress the need for quality control programmes to ensure accurate diagnosis of parasitic infections. Some countries run such programmes at national levels to train laboratories. With globalization of our society, a more centralized approach is necessary. Initiatives like that of the FAO are a major step towards achieving this goal. TS
Protozoal DNA triggers innate immunity
A new study in genetically modified ‘transgenic’ mice provides strong evidence that antigen-specific T helper type 1 (Th1) but not Th2 cells protect mice from lethal infection with Trypanosoma cruzi. S. Kumar and R. Tarleton [(2001) J. Immunol. 166, 4596–4603] found that transfer of Th1 cells to mice before their infection with trypanosomes could dramatically lower parasitemia and increase survival compared to mice that received no cells. By contrast, transfer of Th2 cells resulted in higher parasite levels, greater tissue inflammation and increased mortality. The use of the transgenic mice in combination with specially modified parasites was crucial for this study, because it confirmed the specificity of the T cells for the parasites. SHK
Preference for a reference Diagnosis of parasitic infection is an important aid in the control of infection. However, there is little or no harmonization between different laboratories over which techniques are used to detect infections, making comparison of data difficult. Recently, the use of enzyme-linked immunosorbent assays (ELISA) methods to detect antibodies against trypanosomes was evaluated by the FAO [Rebeski, D. et al. (2001) Vet. Parasitol. 96, 11–50]. Microtitre ELISA plates that were precoated with antigen were shipped to 15 diagnostic laboratories in Africa and Europe. Internal quality control samples were also provided. A detailed analysis of the results obtained in different laboratories allowed the source of errors in the operational performance of the tests to be detected. The
The recognition of protozoal DNA by immune cells could provide an important innate defense mechanism for control of parasitic disease. By culturing macrophages with DNA from Babesia bovis, Trypanosoma cruzi and T. brucei, L. Shoda et al. [(2001) Infect. Immun. 69, 2162–2171] found increased production of pro-inflammatory cytokines IL-12 and TNF-α, in addition to enhanced nitric oxide synthesis. In particular, unmethylated CpG dinucleotides were found to induce strongly macrophage production of these mediators, all three of which are associated with protective immunity against protozoan parasites. Protozoan DNA also has a strong mitogenic effect on B lymphocytes. SHK
311
immunity when formulated with a sugar cube, which is subsequently swallowed. In some cases, to induce protection at the mucosal interface between host and environment, the actual site of vaccine administration is not crucial. Immunity to pathogens that inhabit the intestinal tract can be induced by administration of the vaccine at other mucosal surfaces, such as the mucosae of the nose. However, as with most non-infective vaccines, an adjuvant is required to trigger strong protective responses. Cholera toxin and enterotoxin (LT) are powerful mucosal adjuvants but they are not permitted for human use because of their toxic properties. Recently, non-toxic mutants of LT have been produced and tested for their immunopotentiating effect when combined with a surface antigen of Toxoplasma gondii [SAG1; Bonenfant, C. et al. (2001) Infect. Immun. 69, 1605–1612]. The vaccine preparations were administered intranasally in mice. High-level protection was observed after virulent challenge infection with infectious T. gondii cysts. TS
Trypanosoma brucei’s heel?
Nothing to spit at The identification of an immunosuppressive protein in the saliva of ticks may help explain the pathogenicity of Lyme disease and other tick-borne illnesses. The protein was recently identified in saliva of the hard tick Ixodes scapularis by R. Gillespie et al. [(2001) J. Immunol. 166, 4319–4326]. It has been tagged an ‘interleukin-2 (IL-2) binding factor’ because of its ability to prevent the action of IL-2. A member of the IL family of cytokines, IL-2 normally induces T-cell proliferation and leukocyte activation during the generation of immune responses. By preventing these processes, the IL-2 binding factor effectively increases the survival and infectivity of pathogens introduced with tick saliva. The binding factor is specific for both mouse and human IL-2. SHK
The smell of a Toxoplasma vaccine Non-invasive administration of vaccines is preferred over invasive methods, such as injection. Depending on the type of immune reactivity that is required alternative methods might be applicable. The poliomyelitis vaccine is known for its potential to induce
African sleeping sickness caused by Trypanosoma brucei has devastating effects on the cattle population in Africa. The development of vaccines is hampered by the fact that these parasites have developed a highly efficient system to change their phenotypical appearance known as antigenic variation. The outcome of an infection appears to be the result of the balance between the parasite varying the molecules that constitute the surface coat, and the immune system generating specific antibodies against each variant surface molecule. Apart from vector control, the use of therapeutics is necessary. Researchers have now identified a new enzyme that is crucial for the survival of the parasite [Schnaufer et al. (2001) Science 291, 2159–2162]. The enzyme plays a key role in the RNA-editing process required to obtain mature mitochondrial RNA. Repression of the activity of the enzyme resulted in death of early-stage parasites. The results suggest that
http://parasites.trends.com 1471-4922/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.