Immune responses to Trichinella spiralis and T. pseudospiralis in mice.

A comparison was made of the immunological responses of inbred NIH mice to the intestinal stage of infection with two species of the genus Trichinella, T. spiralis and T. pseudospiralis, which are known to have distinct parasitological and pathological relationships with their hosts. The parameters studied, namely antigen-specific IgG1 and IgG2a antibody responses, mucosal mastocytosis, and levels of the cytokines interferon-gamma (IFN-gamma) and interleukin-5 (IL-5) produced by concanavalin A-pulsed mesenteric node lymphocytes in vitro, were chosen to provide information about the relative activities of the Th1 and Th2 T-helper (Th) lymphocyte subsets. In this high-responder host the time-course of infections was similar, although initial levels of establishment were considerably higher for T. pseudospiralis. Both species elicited mucosal mastocytosis. Distinct differences were seen in the IgG isotype responses. Trichinella spiralis-infected mice produced a predominantly IgG2a response, whereas T. pseudospiralis elicited an IgG1 response. Cytokine release showed infection dose-related suppression of IFN-gamma and enhancement of IL-5. These effects were most marked in T. pseudospiralis-infected mice, i.e. there was an earlier shut-off of IFN-gamma and an earlier switch to IL-5. These data suggest that the two species of Trichinella show a time-related differential activity of Th subsets during the early stages of infection. The possibility that this may reflect antigenic differences between these closely related species or result from parasite-induced immunological-endocrinological changes is discussed.

Humoral and cellular immune response of BALB/c mice to repeated infestations with Ixodes ricinus nymphs.

The capacity of female BALB/c mice to mount an immune response and effective resistance to repeated infestations with I. ricinus nymphs was studied. An anamnestic antibody response and transient in vitro responsiveness of spleen lymphocytes to tick antigens were demonstrated in repeatedly infested mice. On the other hand, the response to concanavalin A--a T-cell mitogen, was suppressed at the same time. In the presented experiment, BALB/c mice did not manifest tick resistance after three successive infestations (with a reinfestation period of 2 weeks). The possibility of an infestation-dependent modulation of immune response in BALB/c mice is discussed.

Lymphocyte proliferation and cytokine production in mice infected with different geographical isolates of Trichinella spiralis.

Antigen-specific proliferative responses and cytokine production were measured in lymphocytes taken from inbred NIH mice infected with different isolates of Trichinella spiralis. Stimulation with muscle larval homogenate antigen produced high proliferative responses, cells responding more strongly to antigen from one isolate (London-L) than to antigens of the other two isolates (Spanish-S and Polish-P). Antigen from the P-isolate elicited relatively poor responses. There was considerable, although variable, cross reactivity between isolate antigens and this was reflected in proliferation to heterologous stimulation. When pulsed with the mitogen Concanavalin A (Con-A) mesenteric lymph node cells (MLNC) produced IFN-gamma on day four post infection but not on day eight. In contrast, production of IL-4 and IL-5 was greatest on day eight. Differences were seen in levels of cytokine production between cells taken from mice infected with different isolates. These data show a sequential activation of Th1 and Th2 cells during infection with T. spiralis isolates, and suggest that the level of activation of each Th subset is influenced by the antigenic characteristics of each isolate.

Lymphocyte, antibody and cytokine responses during concurrent infections between helminths that selectively promote T-helper-1 or T-helper-2 activity.

The influence of Trichinella spiralis on infections with Trichuris muris was studied in non-responder B10.BR mice. Mice infected only with T. muris were unable to expel parasites and had many adult worms 35 days later. Infection with 300 larvae of T. spiralis, given seven or 14 (but not 28) days after T. muris, enabled mice to expel up to 90% of T. muris; expulsion of T. spiralis was not altered. Concurrently infected mice produced less T. muris-specific IgG2a antibody than mice infected with T. muris only, and showed higher proliferative responses when spleen and mesenteric lymph node cells were cultured in vitro with T. muris antigens. When T. spiralis was present mucosal mast cells were generated in T. muris-infected mice, whereas almost no mast cells were seen with only T. muris. Lymphocytes from doubly-infected mice produced significantly more interleukin 4 and 5 (IL-4, IL-5) and significantly less interferon-gamma (IFN-gamma) when stimulated in vitro with Concanavalin A (Con-A) than cells from mice infected with T. muris only. These data demonstrate that B10.BR mice, which in single infections produce a Th1 response to T. muris and develop no protective immunity, can mount a protective T-helper-2 (Th2) response and expel T. muris when concurrently infected with the 'Th2-inducing' nematode T. spiralis.

Nonspecific immunomodulation influences the course and location of Cryptosporidium parvum infection in neonatal BALB/c mice.

The influence of nonspecific immunomodulation with Thymomodulin (a calf thymic extract with immunomodulatory activity) and hydrocortisone on the course and location of Cryptosporidium parvum infection in neonatal BALB/c mice (infected with 10(6) or 10(5) oocysts on day 7 of life) was studied using scanning electron microscopy of the inner surface of different parts of intestine. Daily peroral treatment of suckling mice with 20 mg/kg/day of Thymomodulin for 5 days before inoculation resulted in an earlier peak and earlier termination of cryptosporidial infection when compared with control infected mice. On the other hand, peroral administration of 25 mg/kg of hydrocortisone every second day led to the persistence of cryptosporidial infection in the ileum of immunosuppressed mice until the end of observation (day 15 post infection), whereas only transient infection was observed in the intestine of control infected mice. The location of infection was also altered in hydrocortisone--treated mice--the severe infection was observed in more proximal parts of the intestine (anterior and middle jejunum), whereas no cryptosporidia were found in these parts of the intestine in nontreated infected mice.

Prophylactic and therapeutic immune reconstitution of SCID mice infected with Encephalitozoon cuniculi.

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.

Nonspecific immunomodulation influences resistance of mice to experimental infection with Mesocestoides corti and Ascaris suum.

The influence of nonspecific immunomodulation on the course of experimental infection was examined in larval cestodosis (Mesocestoides corti) and ascaridosis (Ascaris suum) in mice. Immunosuppressive treatment (with azathioprine or hydrocortisone) resulted in a decrease of resistance in both models. The subsequent administration of T-activin to immunosuppressed mice led to the restoration of resistance to a level equal to that of untreated control mice. The administration of different immunomodulators partially protected mice against M. corti (T-activin, thymomodulin) or A. suum (T-activin, thymomodulin, thymosin fr.5, bursa-activin) infection. The protective effect of different treatments did not correlate with the level of specific antibody in the sera of infected mice. These results, which confirmed the decisive role of T-cell immunity in the resistance to the helminth infections, raise the possibility of the use of immunomodulators (thymic preparations) in the immunoprophylaxis of helminthoses.

Influence of thymic preparations on the result of experimental infection with Taenia crassiceps (Zeder, 1800) in ICR mice.

Thymalin (Thymarin) and T-activin--thymic preparations of polypeptidic character--were used for influencing the parasitic infection in a model system mouse--Taenia crassiceps. A single subcutaneous application of 100 micrograms of Thymalin per mouse at the day of infection resulted in a decrease (by 54.9%) in the number of cysticerci in peritoneal cavity of experimental mice compared with the controls. Administration of Thymalin with T. crassiceps larval homogenate at various intervals before and after infection resulted in a statistically significant increase of the level of specific antibodies in the serum of infected mice, this increase, however, did not correlate with the corresponding protective effect. Immunosuppressant azathioprine, injected subcutaneously from 7th to 3rd day preceding infection at a dose of 100 micrograms resulted in a significant increase in the number of T. crassiceps larvae in the peritoneal cavity of experimental mice compared with the controls (by 48.7%). T-activin, injected subcutaneously to mice, immunosuppressed by azathioprine, led to a restoration of resistance of mice to T. crassiceps infection. Subcutaneous application of T-activin alone had a significant protective effect (decrease in cysticerci number by 53.7% in comparison with the controls). Correlation of the level of specific antibodies in the serum of infected mice, value of spleen index and number of T. crassiceps cysticerci in peritoneal cavity of mice was not detected.

Effect of T-activin on the course of experimental infection with Taenia crassiceps (Zeder, 1800) in mice.

T-activin--an immunomodulating preparation of polypeptidic character prepared from calf thymus--was used for influencing the course of infection in a model system mouse-Taenia crassiceps. A single s.c. application of 100 micrograms of T-activin at various intervals before and after infection resulted in a marked decrease in the number of cysticerci in peritoneal cavities of experimental mice (by 47.1-93.6%) compared to the controls. After s.c. application of T-activin and i.p. injection of antigen (crude T. crassiceps larvae homogenate from mice) the decrease in the cystricercus number was still more pronounced than in the mouse groups receiving only T-activin or homogenate (by 76.9% in comparison with 65.5% and 17.0%, respectively). A combination of T-activin with crude T. crassiceps homogenate from rats did not produce the same effect in experimental mice. The protective effect of individual combinations of T-activin with the homogenate does not correlate with the antibody level in the serum of infected mice.