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Role of gamma interferon in cellular immune response against murine Encephalitozoon cuniculi infection
1Department of Medicine and Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. Imtiaz.Khan@dartmouth.edu
Abstract:
Microsporidia are obligate intracellular protozoan parasites that cause a wide variety of opportunistic infection in patients with AIDS. Because it is able to grow in vitro, Encephalitozoon cuniculi is currently the best-studied microsporidian. T cells mediate protective immunity against this parasite. Splenocytes obtained from infected mice proliferate in vitro in response to irradiated parasites. A transient state of hyporesponsiveness to parasite antigen and mitogen was observed at day 17 postinfection. This downregulatory response could be partially reversed by addition of nitric oxide (NO) antagonist to the culture. Mice infected with E. cuniculi secrete significant levels of gamma interferon (IFN-gamma). Treatment with antibody to IFN-gamma or interleukin-2 (IL-12) was able to neutralize the resistance to the parasite. Mutant animals lacking the IFN-gamma or IL-12 gene were highly susceptible to infection. However, mice unable to secrete NO withstood high doses of parasite challenge, similar to normal wild-type animals. These studies describe an IFN-gamma-mediated protection against E. cuniculi infection that is independent of NO production.
Insights
Immune responses to Encephalitozoon cuniculi, an opportunistic parasite, were studied. Gamma interferon (IFN-gamma) mediates protection, while nitric oxide (NO) production is not essential for controlling this infection.
Area of Science:
- Immunology
- Parasitology
- Microbiology
Background:
- Microsporidia are opportunistic intracellular protozoan parasites.
- Encephalitozoon cuniculi is a well-studied microsporidian due to in vitro cultivation.
- T cells are crucial for protective immunity against E. cuniculi.
Purpose of the Study:
- To investigate the role of gamma interferon (IFN-gamma) and nitric oxide (NO) in immunity against Encephalitozoon cuniculi.
- To understand the mechanisms of protective immunity and immune hyporesponsiveness during E. cuniculi infection.
Main Methods:
- Splenocyte proliferation assays in response to irradiated E. cuniculi.
- Assessment of immune response modulation by nitric oxide (NO) antagonists.
- Analysis of resistance to E. cuniculi infection in mice with altered IFN-gamma, IL-12, or NO production.
Main Results:
- A transient hyporesponsiveness to parasite antigen and mitogen was observed during infection, partially reversible by NO antagonists.
- Mice infected with E. cuniculi secreted significant levels of IFN-gamma.
- Neutralization of IFN-gamma or IL-12 abrogated resistance to E. cuniculi.
- Mice lacking IFN-gamma or IL-12 genes were highly susceptible to infection.
- Mice unable to produce NO showed resistance to high parasite doses.
Conclusions:
- IFN-gamma is a critical mediator of protective immunity against Encephalitozoon cuniculi.
- Immunity against E. cuniculi is independent of nitric oxide (NO) production.
- Understanding these immune pathways can inform strategies against opportunistic microsporidian infections.