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PubMed1983

Immunological consequences of intestinal helminth infections in C57BL mice. The effects on lymphoid tissue and reticuloendothelial function.

The characteristics of primary Nematospiroides dubius, mouse-adapted Nippostrongylus brasiliensis and Trichuris muris infections in C57BL mice and their broad effects on lymphoid tissue and reticuloendothelial function have been compared in an attempt to identify correlations between the effects of the parasites and common features of their life cycles. All three parasites increased the size of the spleen and mesenteric node, roughly in proportion to the intestinal worm burden. N. brasiliensis and T. muris caused thymic atrophy, which was not evident with N. dubius even when it was administered intravenously (i.v.) to establish a tissue migration phase. N. brasiliensis accelerated the clearance of I125-labelled polyvinyl pyrrolidone (I125-PVP) from the circulation by increasing uptake by the liver and lungs. N. dubius caused similar increases when given i.v., suggesting that macrophages in these organs are activated by migrating larvae, but did not affect the levels of I125-PVP in circulation. An established intestinal N. dubius infection increased the levels in circulation and in peritoneal cells.

Animals↗
PubMed1983

Immunological consequences of intestinal helminth infections in C57BL mice. Humoral responses to polyvinyl pyrrolidone.

Infection with Trichuris muris eggs or Nematospiroides dubius larvae (orally administered) did not affect IgG or IgM antibody responses to 0 X 2 micrograms polyvinyl pyrrolidone (PVP) (intravenously (i.v.) or intraperitoneally (i.p.)) or 20 micrograms PVP (i.p.) in C57BL mice. However, Nippostrongylus brasiliensis L3 subcutaneously (s.c.) and N. dubius L3 (i.v.) significantly increased responses to PVP (i.p.) so migrating larvae are probably responsible. Similar enhancement was obtained when extracts of N. brasiliensis worms or N. dubius larvae were administered i.p. The activity of N. brasiliensis extract was trypsin-insensitive and unaffected by heat (1 h, 60 degrees). Extracts of A. suum did not cause significant enhancement and BALB/c mice were not affected by N. brasiliensis extract. The possible roles of regulatory T-cells, non-specific mitogenesis and macrophage activation are discussed.

Animals↗
PubMed1983

Immunological consequences of intestinal helminth infections in C57BL mice. Natural and induced responses to sheep erythrocytes.

Nematospiroides dubius, Nippostrongylus brasiliensis and Trichuris muris infections in C57BL mice increased background IgM titres to SRC but not to erythrocytes from other species. However, no cross-reaction between parasite extracts and SRC could be demonstrated and the enhancement was not evident in other strains of mice. There were no comparable rises in total IgM levels, but declining IgM responses to ovalbumin were boosted by N. dubius, so the rise was probably caused by selective expansion of activated clones of cells. N. dubius also increased responses to low doses of SRC given intraperitoneally (i.p.) a few days after infection, whilst optimal SRC doses induced normal responses. In contrast, N. brasiliensis and T. muris often depressed responses to SRC though the effect was variable and the timing of challenge was critical. Thus, whereas the enhancement of natural titres occurs in C57BL mice infected with any of the parasites tested here or in previous studies, the effects on responses to injected SRC depend on the species of parasite.

Animals↗
PubMed1986

Immunological consequences of intestinal helminth infections. Cellular and anamnestic responses to ovalbumin.

Depressed IgG responses to ovalbumin administered with the inflammatory adjuvant, Al(OH)3, have previously been demonstrated in mice immunized 5 to 13 days after infection with Nematospiroides dubius, when the parasite is encysted in the intestinal mucosa or becoming established in the lumen. This report extends these findings to show that primary IgE and delayed-type hypersensitivity (DTH) responses, the generation of antigen-primed cells detectable in syngeneic irradiated recipients or in vitro and the recall of immunological memory are correspondingly impaired. Co-transfer experiments using irradiated recipients demonstrated weak suppressor activity in spleen cells from infected mice which was not attributable to T cells. The results suggest that N. dubius administered before immunization can impair the development of many classes of antigen-primed lymphocytes. The implications of this finding with respect to parasite survival are discussed.

Aluminum Hydroxide↗
PubMed1986

Immunological consequences of intestinal helminth infections: antigen presentation and immunosuppression by peritoneal cells.

The functional characteristics of peritoneal cells (PC's) acquired in response to infection with Nematospiroides dubius were studied to identify changes which could be associated with the high level, long-term survival of this parasite or explain its transient immunosuppressive properties. The number of cells in the peritoneal cavity increased steadily during the infection, and the population displayed a transient hyperresponsiveness to inflammatory stimulation. N. dubius did not affect the ability of antigen-pulsed PC's to induce humoral responses or delayed-type hypersensitivity (DTH) in primed recipients, but lymphoproliferative responses induced in vitro were depressed by PC's from infected donors. In addition, unpulsed PC's from N. dubius-infected mice depressed proliferative responses to parasite antigens by autologous mesenteric lymph node cells. These effects are attributable to increased lymphocytostatic activity in the PC's, which peaked one week after infection and correlated with the expansion of a population of large plastic-adherent vacuolated cells with elevated acid phosphatase activity (activated macrophages). Comparable inhibitory cells did not develop in the same period of time during a short-lived infection with Nippostrongylus brasiliensis.

Aluminum Hydroxide↗
PubMed2001

Interleukin (IL)-18 promotes the development of chronic gastrointestinal helminth infection by downregulating IL-13.

Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th) 2 type response involving interleukin (IL)-4 and IL-13. Here we show that Th1 response-associated susceptibility involves prior activation of IL-18 and caspase-1 followed by IL-12 and interferon (IFN)-gamma in the intestine. IL-18-deficient mice are highly resistant to chronic T. muris infection and in vivo treatment of normal mice with recombinant (r)IL-18 suppresses IL-13 and IL-4 secretion but does not affect IFN-gamma. In vivo treatment of T. muris-infected IFN-gamma-deficient mice with rIL-18 demonstrated that the inhibitory effect of IL-18 on IL-13 secretion is independent of IFN-gamma. Hence, IL-18 does not function as an IFN-gamma-inducing cytokine during chronic T. muris infection but rather as a direct regulator of Th2 cytokines. These results provide the first demonstration of the critical role of IL-18 in regulating Th cell responses during gastrointestinal nematode infection.

Animals↗
PubMed2005

Functional significance of low-intensity polyparasite helminth infections in anemia.

BACKGROUND: We wanted to quantify the impact that polyparasite infections, including multiple concurrent low-intensity infections, have on anemia. METHODS: Three stool samples were collected and read in duplicate by the Kato-Katz method in a cross-sectional sample of 507 children from Leyte, The Philippines. The number of eggs per gram of stool was used to define 3 infection intensity categories--uninfected, low, and moderate/high (M+)--for 3 geohelminth species and Schistosomiasis japonicum. Four polyparasite infection profiles were defined in addition to a reference profile that consisted of either no infections or low-intensity infection with only 1 parasite. Logistic regression models were used to quantify the effect that polyparasitism has on anemia (hemoglobin level <11 g/dL). RESULTS: The odds of having anemia in children with low-intensity polyparasite infections were nearly 5-fold higher (P = .052) than those in children with the reference profile. The odds of having anemia in children infected with 3 or 4 parasite species at M+ intensity were 8-fold greater than those in children with the reference profile (P < .001). CONCLUSION: Low-intensity polyparasite infections were associated with increased odds of having anemia. In most parts of the developing world, concurrent infection with multiple parasite species is more common than single-species infections. This study suggests that concurrent low-intensity infections with multiple parasite species result in clinically significant morbidity.

Adolescent↗
PubMed1992

Parasitic helminth infection and cognitive function in school children.

The study examines the effect of moderate to high worm burdens of Trichuris trichiura infection on the cognitive functions of 159 school children (age 9-12 years) in Jamaica, using a double-blind placebo-controlled protocol. Results were evaluated by using a forward-stepwise multiple linear regression. Removal of worms led to a significant improvement in tests of auditory short-term memory (p less than 0.017; p less than 0.013), and scanning and retrieval of long-term memory (p less than 0.001). Nine weeks after treatment, there were no longer significant differences between the treated children and an uninfected Control group in these three tests of cognitive function. It is concluded that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy.

Albendazole↗
PubMed1988

Population ecology of intestinal helminth infections in human communities.

The distribution of worm burdens in human populations is a major determinant of both the dynamics of transmission and the level of community morbidity. The distribution exhibits convexity with host age, which appears to correlate with exposure in the young age-classes but not in adults, and may be evidence for the development of an acquired immune response. The distribution between individuals is typically overdispersed. Individuals are predisposed to high (or low) intensity of infection and to a correspondingly high (or low) rate of acquisition of infection. A major epidemiological question is whether this reflects individual differences in environmental exposure or susceptibility. Environmental studies that have observed clustering of intense infection in particular households are supportive of either mechanism. Individual host behaviours that predispose to infection have an overdispersed distribution and may alone, or as compounding factors, generate the observed distribution of infection intensity. Factors such as host nutrition and physiology may modify host immune-responsiveness and hence susceptibility. Preliminary evidence suggests correlates between infection intensity and HLA class II antigens, and tentatively implies a genetic factor in susceptibility. These findings suggest that further understanding of the relative importance of environmental factors and resistance to the acquisition of intense infection is dependent upon a multidisciplinary approach to epidemiological field study.

Ecology↗
PubMed1984

Immunological consequences of intestinal helminth infections. Humoral responses to ovalbumin.

Humoral responses to ovalbumin (OA) administered i.p. with Al(OH)3 were depressed in C57BL mice immunized 5-13 days after infection with N. dubius, but not N. brasiliensis or T. muris. These two parasites induced elevated IgM responses, possibly as a result of systemic contact with parasite larvae or debris since i.v. administered N. dubius also increased IgM titres to OA. Depression of anti-OA IgG titres by N. dubius was also observed in infected BALB/c and CBA mice given OA-Al(OH)3 (i.p.), but not in C57BL mice given OA-Al(OH)3 (s.c.), OA-FCA (i.p. or s.c.), or OA-B, pertussis (i.p.). These findings suggest that local effects of N. dubius within the peritoneum reduce the adjuvanticity of Al(OH)3, resulting in depressed responses to OA-Al(OH)3.

Animals↗
PubMed1993

Altered expression of mast cell proteases in the rat. Quantitative and immunohistochemical analysis of the distribution of rat mast cell proteases I and II during helminth infection.

Expression of mast cell granule protease is regulated in a tissue-specific fashion in the rat. The granule chymases rat mast cell proteases I and II (RMCP I and II) predominate in non-mucosal and mucosal sites, respectively. Intestinal mastocytosis, a T cell-mediated phenomenon associated with enteric nematodiasis, is accompanied by massive local expression of RMCP II and by release of this protease systemically into blood. The present observations, where both RMCP I and II have been quantified by ELISA and immunolocalized by paired fluorescence, show that the expression of both proteases in parasitized rats is profoundly altered at sites distant from infection. Thus, RMCP II-containing cells are recruited to liver and thymus, and in the thymus there is a > 2-fold increase in concentration of RMCP I. The latter protease is depleted from bone marrow and mesenteric lymph node early during infection, but concentrations of RMCP I in trachea/larynx, lung, and skeletal and cardiac muscle are increased. Increased mast cell counts in intestine, lung and liver are highly correlated with tissue concentrations of RMCP II.

Animals↗