Heligmosomoides polygyrus (=Nematospiroides dubius): suppression of antibody response to orally administered sheep erythrocytes in infected mice.

Mice infected with 200 to 300 Heligmosomoides polygyrus had reduced serum hemagglutinin titers following a series of oral inoculations of sheep erythrocytes (SRBC) when compared to similarly inoculated uninfected mice. Study of antibody-producing cells by the indirect hemolytic plaque technique demonstrated a low splenic response to oral immunization in which IgA predominated. No alteration was evident in the proportions of antibody-containing cells in the different Ig classes with infection. Comparison of the immune response to oral and intraperitoneal routes of SRBC inoculation in infected and uninfected mice demonstrated a similar reduction in antibody titer with both routes of inoculation, although immunosuppression following intraperitoneal inoculations was not consistantly observed. The data are discussed in relation to the influence of the helminth infection on intestinal immune response and systemic immune response.     

Oxygen uptake in mice infected with Trichinella spiralis

Oxygen consumption, rectal temperature, and the level of activity in mice infected with Trichinella spiralis were significantly reduced below that seen in uninfected controls for periods of time during the first 30 days following infection. The differences in oxygen consumption between controls and infected animals were evident throughout the 24-hr period comprising day 7 postinfection. Both oxygen consumption and rectal temperature increased with decreasing level of infection. These changes in oxygen consumption, rectal temperature, and activity are discussed in terms of pathophysiologic and immunopathologic changes known to occur during the course of infection.     

Trypanosome-induced suppression of responses to Trichinella spiralis in vaccinated mice.

Mice vaccinated against the gastro-intestinal (GI) nematode Trichinella spiralis by injection of muscle larval homogenate antigen express a strong immunity to subsequent infection, reflected in earlier expulsion of adult worms from the intestine and reduced female worm fecundity. Infection with Trypanosoma brucei at the time of vaccination, or at the time of infection with T. spiralis, significantly reduced the level of immunity expressed, the effect being greatest when vaccination and T. brucei infection were given together. Trypanosome infection reduced T. spiralis-specific antibody responses in vaccinated mice, the effect being most apparent against IgM, IgG1 and IgG2b, and ablated the eosinophil response to T. spiralis. In vaccinated mice infected with both trypanosomes and T. spiralis, the proliferative responses of lymphocytes to the mitogen Con A or to T. spiralis antigen were much lower than in vaccinated mice infected only with the nematode. Whereas cells from mice infected only with T. spiralis produced the cytokine IL-4 and little or no IFNgamma when stimulated in vitro, cells from animals infected with T. spiralis and with trypanosomes released large amounts of IFNgamma but no IL-4. These observations are consistent with the known, IFNgamma-dependent, nitric-oxide-mediated suppressive effects of trypanosomes on lymphocyte function and the Th1 bias associated with these infections, both of which reduce the effectiveness of the Th2-mediated responses involved in immunity against GI nematode infections. The data are discussed in the context of the possible use of vaccines against GI nematodes in ruminants in countries where concurrent trypanosome-GI nematode infections are widespread.     

Trichinella spiralis: inhibition of sheep hemagglutinins in mice

One hundred and twenty-four mice were injected intraperitoneally with sheep red blood cells. The mice had been previously either orally inoculated with T. spiralis (16 mice), or injected intraperitoneally during 7 consecutive days with normal saline (12 mice), normal mouse serum (6 mice), or infected mouse serum (6 mice), normal rabbit serum (6 mice), sera from lightly (36 mice) or heavily infected rabbits (36 mice), and rabbit anti-lymphocyte serum (6 mice). The homologous serum clearly demonstrated an immunosuppressive effect on the production of sheep hemagglutinins; however, it was impossible to conclude that heterologous serum has such an activity since the normal rabbit serum used as control demonstrated the same activity. The inhibition of hemagglutinin production has also been observed in mice infected with T. spiralis. The presence of a suppressive agent released by the parasite or antigenic competition is discussed as the possible mediator of immunological unresponsiveness.     

Trichinella spiralis: strong antibody response to a 49 kDa newborn larva antigen in infected rats

In this work, we analyzed the kinetics of anti-Trichinella spiralis newborn larva (NBL) antibodies (Ab) and the antigenic recognition pattern of NBL proteins and its dose effects. Wistar rats were infected with 0, 700, 2000, 4000 and 8000 muscle larvae (ML) and bled at different time intervals up to day 31 post infection (p.i.). Ab production was higher with 2000 ML dose and decreased with 8000, 4000 and 700 ML. Abs were not detected until day 10, peaked on day 14 for the 2000 ML dose and on day 19 for the other doses and thereafter declined slowly from 19 to 31 days p.i. In contrast, Abs to ML increased from day 10, peaked on day 19 and remained high until the end of the study. Abs bound strongly at least to three NBL components of 188, 205 and 49 kDa. NBL antigen of 188 and 205 kDa were recognized 10-26 days p.i. and that of 49 kDa from day 10 to day 31 p.i. A weak recognition towards antigens of 52, 54, 62 and 83 kDa was also observed during the infection. An early recognition of 31, 43, 45, 55, 68 and 85 kDa ML antigens was observed whereas the response to those of 43, 45, 48, 60, 64 and 97 kDa (described previously as TSL-1 antigens) occurred late in the infection. A follow-up of antigen recognition up to day 61 with the optimal immunization dose (2000 ML) evidenced a decline of Ab production to the 49 kDa NBL antigen 42 days p.i., which suggested antigenic differences with the previously reported 43 kDa ML antigen strongly recognized late in the infection. To analyze the stage-specificity of the 49 kDa NBL antigen, polyclonal antibodies (PoAb) were obtained in rats immunized with 49 kDa NBL antigen. PoAb reacted strongly with the 49 kDa NBL component in NBL total soluble extract but no reactivity was observed with soluble antigen of the other T. spiralis stages. Albeit with less intensity, the 49 kDa component was also recognized by PoAb together with other antigens of 53, 97 and 107 kDa, in NBL excretory-secretory products (NBL-ESP). Thus, our results reveal differences in the kinetics of anti-NBL and ML Ab responses. While anti-NBL Abs declined slowly from day 19 until the end of the experiment, Abs to ML antigen remained high in the same period. It is remarkable the optimal Ab response to NBL antigens with 2000 ML infective dose and the reduced number of NBL antigens identified throughout the experimental T. spiralis infection, standing out the immunodominant 49 kDa antigen. Interestingly, this antigen, which was prominently expressed in NBL somatic proteins, was also detected in NBL-ESP.     

Biphasic hypothermia in mice infected with a parasitic nematode, Trichinella spiralis.

In BALB/c mice infected with Trichinella spiralis, changes in body temperature (Tb) were observed over 35 days after the infection. T. spiralis infection induced hypothermia two times at 7 and 28 days after infection. The initial decrease persisted for about one week with a peak (37.1 +/- 0.62 degrees C) around 10 days after the infection, while the later phase persisted for at least one week. Both 10 and 35 days after the infection, there were remarkable decreases in Tb. The serum glucose level of infected mice at 10 days was significantly (p < 0.01) decreased compared with that of control mice at the same number of days, while the level in infected mice at 35 days was not decreased. Moreover, the later phase of hypothermia was prevented by the cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.), while the initial phase was not. We conclude that hypothermia was caused by two different mechanisms, involving the effects of hypoglycemia and prostaglandins.     

Studies on accessory cells in the adoptive antibody response to sheep erythrocytes in mice

CBA mice irradiated 3 days prior to injection of syngeneic nonadherent spleen cells and high numbers of SRBC contained approximately ten times more splenic direct plaque forming cells than mice irradiated immediately prior to transfer. This was not true of C57B1 mice. Increased responses in the CBA mice were shown to be dependent upon accessory cells (A cells). The results suggest that A cells are affected differently by irradiation in different strains of mice.     

The response of the intestinal epithelium in B10.A mice to infection with Trichinella spiralis

Previous studies on intestinal trichinosis have dealt mainly with areas other than the intestinal epithelium. Since the epithelium is now known to be the parasite's habitat, its response to infection is important. Infection with Trichinella spiralis in immunologically slow-responding B10.A mice was associated with crypt hyperplasia and villus atrophy. With similar infection levels in both primary and challenge infections, there was no difference in the maximal degree of atrophy or hyperplasia between the 2 groups. However, challenged mice underwent these mucosal changes in about half the time. Expulsion of worms always occurred during regeneration of the intestinal epithelium suggesting that the host's defense mechanism of altering the kinetics of the epithelium was not the prime factor causing expulsion. Pulse labelling of enterocytes with [3H] thymidine showed that there was no significant increase in the relative size of the proliferation zone. This indicates that the crypt cell output was not altered by this parasite. Atrophy of the villus was analysed with respect to its 3-dimensional shape. There was a decrease in both height and width of the villus but not thickness. Thus, there is a real decrease in the size of the enterocyte population per villus. Histochemical staining of the enterocyte brush border by an alkaline phosphatase method showed that (1) hyperplastic crypts have an enlarged maturation zone and (2) the villus epithelium is composed entirely of mature cells. The distribution of the nematode population was compared to these changes in the intestine. Trichinella spiralis showed a marked anteriad (distal to proximal) migration prior to expulsion. Thus, utilizing a novel approach to study intestinal trichinosis, the response of the mucosal epithelium has been characterized.     

Immune responses to Trichinella pseudospiralis and Trichinella spiralis in mice

Primary infections with Trichinella pseudospiralis and Trichinella spiralis were followed in rapid- (NIH) and slow- (B10G) responder strains of mice. Expulsion of T. pseudospiralis was slower in both strains, but markedly so only in slower responder B10G mice. Blast cell activity in the mesenteric lymph nodes of the mice correlated with the expulsion patterns. In NIH mice, both parasites stimulated a strong response by day 8 of infection and activity had returned to control levels by day 11. In B10G mice, T. spiralis elicited an earlier peak response (day 12) than T. pseudospiralis (day 18), but in both, activity returned to control levels by day 21. Immunity to T. pseudospiralis and T. spiralis could be stimulated in NIH mice by prior infection with either parasite, by injection of T. spiralis larval antigen and by adoptive transfer of immune mesenteric lymph node cells taken from mice infected with either parasite. This extensive cross reactivity, and the differences seen during primary infections, are discussed in relation to the biology and specific identity of the two worms.