Immunological interactions between 2 common pathogens, Th1-inducing protozoan Toxoplasma gondii and the Th2-inducing helminth Fasciola hepatica.
BACKGROUND
The nature of the immune response to infection is dependent on the type of infecting organism. Intracellular organisms such as Toxoplasma gondii stimulate a Th1-driven response associated with production of IL-12, IFN-gamma, nitric oxide and IgG2a antibodies and classical activation of macrophages. In contrast, extracellular helminths such as Fasciola hepatica induce Th2 responses characterised by the production of IL-4, IL-5, IL-10 and IgG1 antibodies and alternative activation of macrophages. As co-infections with these types of parasites commonly exist in the field it is relevant to examine how the various facets of the immune responses induced by each may influence or counter-regulate that of the other.


RESULTS
Regardless, of whether F. hepatica infection preceded or succeeded T. gondii infection, there was little impact on the production of the Th1 cytokines IL-12, IFN-gamma or on the development of classically-activated macrophages induced by T. gondii. By contrast, the production of helminth-specific Th2 cytokines, such as IL-4 and IL-5, was suppressed by infection with T. gondii. Additionally, the recruitment and alternative activation of macrophages by F. hepatica was blocked or reversed by subsequent infection with T. gondii. The clinical symptoms of toxoplasmosis and the survival rate of infected mice were not significantly altered by the helminth.


CONCLUSIONS
Despite previous studies showing that F. hepatica suppressed the classical activation of macrophages and the Th1-driven responses of mice to bystander microbial infection, as well as reduced their ability to reject these, here we found that the potent immune responses to T. gondii were capable of suppressing the responses to helminth infection. Clearly, the outcome of particular infections in polyparasitoses depends on the means and potency by which each pathogen controls the immune response.
Miller
Catherine M D
CM
Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, New South Wales, Australia. Catherine.Miller@uts.edu.au
Smith
Nicholas C
NC
Ikin
Rowan J
RJ
Boulter
Nicola R
NR
Dalton
John P
JP
Donnelly
Sheila
S
D000208:Acute Disease; D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005210:Fasciola hepatica / Q000276:immunology*; D005211:Fascioliasis / Q000097:blood / Q000150:complications / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008262:Macrophage Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000469:parasitology; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000097:blood / Q000150:complications / Q000276:immunology*
D000909:Antibodies, Helminth; D000913:Antibodies, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G