Related Experiment Videos
Different roles for interleukin-4 during the course of Toxoplasma gondii infection
C W Roberts1, D J Ferguson, H Jebbari
1Department of Immunology, University of Strathclyde, Glasgow, United Kingdom.
Abstract:
The course of Toxoplasma gondii infection from initiation of disease perorally until day 28 postinfection was compared between interleukin-4 (IL-4) gene knockout (IL-4-/-) mice and their wild-type (IL-4+/+) counterparts on a disease-susceptible genetic background. The rate of mortality was significantly greater in mice deficient in Il-4 than in the immunocompetent controls. Although levels of T. gondii-specific spleen cell proliferation measured in vitro were similar between groups at all time points examined throughout infection, the quantities of cytokines released into the culture supernatant differed. Culture supernatants from spleen cells derived from IL-4-deficient mice contained significantly more gamma interferon than those derived from IL-4+/+ mice at day 7 postinfection. Conversely, IL-10 production was significantly greater from the spleen cells derived from wild-type mice at day 28 postinfection. Splenocytes from both groups of mice had a marked inhibition of proliferation in response to soluble tachyzoite antigen as well as reduced proliferation in response to concanavalin A between days 7 and 14 postinfection and marked proliferation on days 21 and 28 postinfection. At day 28 postinfection, histological examination of the brains indicated that IL-4+/+ mice had more severe pathological changes and more cysts than IL-4-/- mice. In addition, although many nonencysted single organisms were present in IL-4+/+ mice within both necrotic lesions and microglial nodules, few nonencysted parasites were found, and no necrotic lesions were present in IL-4-deficient animals. These results suggest that the observed reduction in mortality during the early acute phases of infection may be due to the down-regulatory effects of Il-4 or associated Th2-derived products on proinflammatory cytokines such as gamma interferon. However, the long-term effects of IL-4 are detrimental, possibly because of the ability of this cytokine to inhibit proinflammatory antiparasitic products. This may explain the increased parasite multiplication with cysts observed in the brains of IL-4+/+ mice.
Insights
Interleukin-4 (IL-4) deficiency in mice increased mortality from Toxoplasma gondii infection, suggesting IL-4
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Toxoplasma gondii is an opportunistic parasite causing toxoplasmosis.
- Interleukin-4 (IL-4) plays a complex role in immune responses to parasitic infections.
Purpose of the Study:
- To investigate the role of IL-4 in the host's immune response and disease progression during T. gondii infection.
- To compare the outcomes of T. gondii infection in IL-4 gene knockout mice versus wild-type mice.
Main Methods:
- Comparison of mortality rates between IL-4 knockout (IL-4-/-) and wild-type (IL-4+/+) mice.
- In vitro measurement of T. gondii-specific spleen cell proliferation and cytokine production (gamma interferon, IL-10).
- Histological examination of brain tissue for parasite load, lesions, and cysts.
Main Results:
- IL-4-/- mice exhibited significantly higher mortality rates compared to IL-4+/+ mice.
- Spleen cells from IL-4-/- mice produced more gamma interferon early in infection, while IL-4+/+ mice produced more IL-10 later.
- IL-4+/+ mice showed more severe brain pathology, increased parasite cysts, and non-encysted parasites compared to IL-4-/- mice.
Conclusions:
- Early reduction in mortality in IL-4 deficient mice may be due to IL-4's down-regulatory effect on pro-inflammatory cytokines like gamma interferon.
- Long-term detrimental effects of IL-4 may arise from its inhibition of anti-parasitic responses, leading to increased parasite multiplication.
- IL-4 has a dual role in T. gondii infection, potentially protective early but detrimental later in the infection course.