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Prophylactic and therapeutic immune reconstitution of SCID mice infected with Encephalitozoon cuniculi
J Hermánek1, B Koudela, Z Kucerová
1Institute of Parasitology, Academy of Sciences of the Czech Republic, Ceské Budĕjovice.
Abstract:
Severe combined immunodeficient (SCID) mice develop lethal infections, resembling opportunistic microsporidiosis of immunocompromised patients, after intraperitoneal (i.p.) inoculations of spores of Encephalitozoon cuniculi. In the present study, SCID mice reconstituted i.p. with 5 x 10(7) spleen cells from naive adult BALB/c mice 14 days prior to the i.p. injection of 10(7) spores were completely resistant to the infection, whereas control infected SCID mice developed clinical disease and died within 17 days post infection (DPI). In another experiment, SCID mice infected i.p. with 10(7) spores of E. cuniculi and after that (on DPI 7) injected i.p. with 5 x 10(7) spleen lymphocytes isolated from immune adult BALB/c mice were partially protected against the parasite (40% of the reconstituted mice survived). In both experiments, high levels of parasite-specific serum antibodies (mostly of the IgG-isotype) were detected in the infected immunocompetent BALB/c mice, whereas virtually no antibodies were found in the infected SCID mice. However, SCID mice reconstituted with either naive spleen cells or immune lymphocytes revealed humoral immune responses comparable with those of immunocompetent mice.
Insights
Adoptive transfer of spleen cells confers resistance against Encephalitozoon cuniculi infection in severe combined immunodeficient (SCID) mice. This reconstitution restored protective immunity and humoral responses against opportunistic microsporidiosis.
Area of Science:
- Immunology
- Parasitology
- Infectious Diseases
Background:
- Severe combined immunodeficient (SCID) mice are susceptible to lethal Encephalitozoon cuniculi infections, mirroring opportunistic microsporidiosis in immunocompromised humans.
- SCID mice lack adaptive immunity, making them a model to study the role of specific immune components in host defense.
Purpose of the Study:
- To investigate the protective effects of adoptive immune cell transfer on E. cuniculi infection in SCID mice.
- To evaluate the restoration of humoral immune responses following reconstitution with naive or immune spleen cells.
Main Methods:
- SCID mice were reconstituted with naive or immune BALB/c spleen cells prior to or after infection with E. cuniculi.
- Parasite load, clinical signs, survival rates, and parasite-specific antibody production (IgG) were assessed.
Main Results:
- Complete resistance was observed in SCID mice reconstituted with naive spleen cells before infection.
- Partial protection (40% survival) was achieved when SCID mice were reconstituted with immune lymphocytes after infection.
- Reconstituted SCID mice exhibited restored humoral immune responses, including high levels of parasite-specific IgG antibodies, comparable to immunocompetent mice.
Conclusions:
- Adoptive transfer of spleen cells can restore protective immunity against E. cuniculi in SCID mice.
- Both naive and immune spleen cells can reconstitute humoral immunity, suggesting the importance of B cell function and antibody production in controlling microsporidiosis.