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PubMed2005

Successive changes in tissue migration capacity of developing larvae of an intestinal nematode, Strongyloides venezuelensis.

Infective larvae of an intestinal nematode, Strongyloides venezuelensis, enter rodent hosts percutaneously, and migrate through connective tissues and lungs. Then they arrive at the small intestine, where they reach maturity. It is not known how S. venezuelensis larvae develop during tissue migration. Here we demonstrate that tissue invasion ability of S. venezuelensis larvae changes drastically during tissue migration, and that the changes are associated with stage-specific protein expression. Infective larvae, connective tissue larvae, lung larvae, and mucosal larvae were used to infect mice by various infection methods, including percutaneous, subcutaneous, oral, and intraduodenal inoculation. Among different migration stages, only infective larvae penetrated mouse skin. Larvae, once inside the host, quickly lost skin penetration ability, which was associated with the disappearance of an infective larva-specific metalloprotease. Migrating larvae had connective tissue migration ability until in the lungs, where larvae became able to settle down in the intestinal mucosa. Lung larvae and mucosal larvae were capable of producing and secreting adhesion molecules.

Animals↗
PubMed2006

The reversibility of constraints on size and fecundity in the parasitic nematode Strongyloides ratti.

The size and fecundity of parasitic nematodes are constrained by the host immune response. For the parasitic nematode of rats, Strongyloides ratti, parasitic females infecting immunized rats are smaller and less fecund than those infecting naïve rats. Here, we investigated whether these constraints on size and fecundity are life-long. This was done by comparison of worms from different immunization and immunosuppression regimes. It was found that the per capita fecundity of parasitic females of S. ratti is fully reversed, but that their size is only partially reversed, if previously immunized hosts are subsequently immunosuppressed, suggesting that fecundity is not subject to life-long constraints. The host immune response also resulted in allometric changes in the parasitic females. The significance of these results with respect to the growth and control of nematode fecundity are discussed.

Animals↗
PubMed1997

Early increase of gut intraepithelial mast cell precursors following Strongyloides venezuelensis infection in mice.

The time-course of differentiation/proliferation of mast cells in gut epithelium was investigated in mice infected with the nematode Strongyloides venezuelensis. After infection, expression of proliferating cell nuclear antigen increased in gut intraepithelial mast cells on days 7 to 11, followed by an increase in the number of intraepithelial mast cells from days 11 to 14. Mast cell precursors were defined as cells that formed mast cell colonies in methylcellulose culture. After infection, the numbers of mast cell precursors in the population of gut intraepithelial mononuclear cells (IEMNC) increased significantly on day 3 and returned to the pre-infection level by day 7. Mast cell precursors in Peyer's patches, mesenteric lymph nodes (MLN), and spleen also increased from day 7 p.i. Production of IL-3 and IL-4 in MLN and spleen were increased between 7 and 11 days p.i. These results show that murine intestinal mastocytosis is initiated by an early increase in mast cell precursor number in the gut epithelium followed by proliferation/differentiation of mast cells. Mast cell precursor numbers increased even before the production of IL-3 and IL-4 in MLN and spleen, suggesting that some local factors might be involved in this phenomenon.

Animals↗
PubMed1998

Spatial and discrimination learning in rodents infected with the nematode Strongyloides ratti.

Recent work has shown that mice with subclinical parasitic infections suffer impaired spatial learning and memory, as assayed in an open-field water maze. Although the mechanism underlying this effect is not clear, the phenomenon has been reported following infection with both a protozoan parasite (Eimeria vermiformis) and a gastrointestinal nematode (Heligmosomoides polygyrus). In a variety of experiments, we examined the effects of a different gastrointestinal nematode, Strongyloides ratti, on the ability of rats and mice to learn a spatial or a discrimination task. Animals were tested at various stages post-infection, with different levels of infection, using different lines of S. ratti and with varying experimental protocols. All animals learned the tasks, but we found no evidence of an effect of S. ratti infection on learning or memory. Even rats infected with approximately 5000 S. ratti larvae, a dose which has an impact on rat body size, showed no deficit in learning ability. Various reasons for the conflict between our results and those previously reported for E. vermiformis and H. polygyrus are discussed. Our results show that impaired learning and memory following parasitic infection is not a ubiquitous or at least easily replicated phenomenon.

Analysis of Variance↗
PubMed1999

Heterogeneity in the distribution of Strongyloides ratti infective stages among the faecal pellets of rats.

The distribution of helminth parasites within their host population is usually overdispersed and can be described by the negative binomial distribution. The causes of this overdispersion are poorly understood, but heterogeneity in the distribution of infective stages within the environment has been implicated as a possible factor. Here we describe the distribution of infective stages of the rat intestinal nematode parasite Strongyloides ratti among the faecal pellets of its host. The distribution of infective stages between faecal pellets is overdispersed and well described by the negative binomial distribution. This overdispersion increases during the course of infection and occurs over a range of infection intensities. Overdispersion of nematode infective stages among faecal pellets may result in increased spatial heterogeneity of the infective stages in the environment and thus may contribute to the generation of overdispersion of adult parasitic stages. In addition, these findings raise important issues regarding the accurate quantification of helminth egg counts from faecal samples.

Animals↗
PubMed1999

A second peak of egg excretion in Strongyloides ratti-infected rats: its origin and biological meaning.

In Strongyloides ratti-infected rats, 2 peaks of egg excretion were observed; a large one with maximum egg production on days 7-8 of infection and a small more inconspicuous one around day 25. The second peak, which had been ignored in most studies, was produced by adults in the caecum and the colon. The adults were larger in length and had more embryonated eggs in the uterus compared with adults in the small intestine at day 25 post-infection. It is suggested that parasitic adults once expelled from the small intestine resettle and recover in the large intestine. Filter paper faecal culture carried out for 9 days at different days post-infection revealed that the total number of infective larvae that developed during the second peak was twice the number that developed during the first peak, despite the fact that total egg output during the second peak was less than one twentieth of the first peak. The results suggest that the small second peak was as important as the first one in the transmission of S. ratti.

Animals↗
PubMed2000

The evolutionary ecology of host-specificity: experimental studies with Strongyloides ratti.

Factors constraining the evolution of host-specificity were investigated using a gastrointestinal parasitic nematode, Strongyloides ratti. S. ratti is a natural parasite of rats which can also reproduce, with decreased success, in laboratory mice. Observed host-specificity arose from lower establishment, reduced per capita fecundity and more rapid expulsion of parasites from mice relative to rats. Variation in the efficacy of thymus-dependent immunity between host species (rats and mice) was insufficient to explain the majority of the observed differences in parasite establishment and reproductive success. The role of natural selection in determining host-specificity was addressed using experimental selection followed by reciprocal fitness assays in both host species. Experimental selection failed to modify the host-specificity of S. ratti to any measurable degree, suggesting either a lack of genetic variation for this trait or the involvement of as yet unidentified factors underlying the differences in S. ratti fitness in rats and mice respectively. These results are discussed in relation to competing theoretical models of ecological specialization, host immunology and previous attempts to experimentally alter the host-specificity of parasitic nematodes.

Animals↗
PubMed2002

Chronic Strongyloides stercoralis infection in Laotian immigrants and refugees 7-20 years after resettlement in Australia.

During the period 1974-91 large numbers of Southeast Asian immigrants and refugees were resettled in Western countries, including Australia. Health screening during this period demonstrated that intestinal parasite infections were common. A cross-sectional survey of 95 Laotian settlers who arrived in Australia on average 12 years prior to the study was conducted to determine if chronic intestinal parasite infections were prevalent in this group. Twenty-three participants had positive Strongyloides stercoralis test results (22 with positive serology, including I with S. stercoralis larvae detected in faeces and another with larvae and equivocal serology). Of these 23 participants, 18 (78%) had an elevated eosinophil count. Two patients had eggs of Opisthorchis spp. identified by faecal microscopy. The detection of chronic strongyloidiasis in Laotian settlers is a concern because of the potential serious morbidity associated with this pathogen.

Adolescent↗
PubMed1982

Strongyloides ratti infections in congenitally hypothymic (nude) mice.

The course of infection with Strongyloides ratti was examined in congenitally hypothymic CBA/H, C57Bl/6 and BALB/c nude mice. The intensity of infection and the duration of faecal larval excretion were both increased in nude mice when compared with intact mice. Adult worms persisted in the small intestine of nude mice for at least 6 weeks. Greater worm burdens were found in such mice after subcutaneous injection as compared with percutaneous infection. Hypothymic mice did not acquire resistance to re-infection. It is concluded that both the spontaneous expulsion of worms in primary infection and resistance to challenge infection are T cell-dependent events. Autoinfection was not seen.

Animals↗
PubMed1983

The location of antigenic sites on the surface of the nematode parasite Strongyloides ratti reactive to antibody-directed cellular cytotoxicity from both macrophages and eosinophils from the natural host.

Heat-treated and untreated sera from rats immune to Strongyloides ratti are capable of arming both immune and non-immune macrophages and eosinophils in vitro. These cells are capable of killing larvae of the parasite. Electron microscopy has indicated multi-point attachment of the cells to the epicuticular transverse grooves of the larvae within 4 and 24 h of incubation at 37 degrees.

Animals↗
PubMed1985

Interactions of Strongyloides ratti free-living and skin-penetrated infective larvae and parasitic adults with serum and cells in vitro.

When Strongyloides ratti free-living infective larvae were incubated with peritoneal exudate cells from normal or previously infected mice, cell attachment occurred only in the presence of normal (NMS) or immune mouse serum (IMS). This non-specific effect was transitory with larvae being alive and free of cells 24 h after incubation. Cell attachment was mediated by complement. When incubated with infective larvae which had penetrated mouse skin, both normal and immune cells attached to larvae in the absence of serum. This effect was again transitory except when immune cells or immune serum were present, indicating a specific immunological mechanism. Again, larvae remained viable. When incubated with isolated parasitic adult worms, persistent cell attachment occurred in the presence of immune serum, immune cells or both, but all worms remained viable. This system provides a means for investigating the mechanisms of resistance to reinfection in strongyloidiasis.

Adhesiveness↗
PubMed1987

Antigenic analysis of Strongyloides ratti infective larvae and adult worms.

The protein composition of Strongyloides ratti infective larvae and adult worms extracted sequentially in water, sodium deoxycholate and sodium dodecyl sulphate (SDS) and their excretory/secretory products were analysed by both one- and two-dimensional SDS-polyacrylamide gel electrophoresis. While many bands common to all preparations and both stages of the worm were seen, a number of bands unique to each stage and preparation were identified. Western blot analysis of these larval and adult preparations for reaction with IgG and IgM antibodies in hyperimmune mouse sera revealed a large number of antigens. These data provide a framework for analysis of protective and diagnostically useful antigens.

Animals↗
PubMed1993

Transient retention of Strongyloides ratti in the caecal mucosa during infection in mice.

Adult worms of Strongyloides ratti, after elimination from the small intestine, were retained in the caecum for at least three days during the infection in mice. This retention was a biological event but not due to a simple mechanical trapping in faeces. In addition to the local mucosal mastocytosis, eosinophil infiltration was remarkable in the caecum around day 10 when adult worms were expelled from there.

Animals↗
PubMed2006

Interleukin-3 and c-Kit/stem cell factor are required for normal eosinophil responses in mice infected with Strongyloides venezuelensis.

To evaluate the potential roles of Interleukin-3 (IL-3) and c-Kit, the tyrosine kinase receptor for stem cell factor (SCF), in eosinophil responses in vivo, we examined eosinophil numbers in uninfected or nematode-infected wild-type mice, IL-3-/- mice, and IL-3-/- mice that also have a marked reduction in SCF/c-Kit signaling (ie, Kit(W)/Kit(W-v), IL-3-/- mice). We found no significant differences in the numbers of eosinophils in the blood, bone marrow or various tissues of IL-3-/- vs IL-3+/+ mice, either at baseline or after the induction of bone marrow, blood or tissue eosinophilia in response to infection with Strongyloides venezuelensis (S.v.) or Nippostrongylus brasiliensis (N.b.). However, in mice with markedly impaired SCF/c-Kit signaling, IL-3 contributed significantly to the increased numbers of eosinophils that were observed in multiple tissues during S.v. infection, but not during infection with N.b.

Animals↗
PubMed2002

The role of B cells in immunity against larval Strongyloides stercoralis in mice.

The objective of this study was to examine the role of B cells in primary and challenge infections of larval Strongyloides stercoralis in mice. Two strains of B-cell deficient mice were used in these studies, microMT mice that lack all B cells and Xid mice that lack B-1 cells. Primary immune responses in microMT mice were sufficient to eliminate all parasites within 1 week after infection. Immunized microMT and Xid mice, however, were unable to kill challenge parasites at 24 h post infection, the time that they were eliminated in immunized wild-type mice. This was despite having a significant increase in interleukin-5 secreting cells and high numbers of eosinophils in the microenvironment of the challenge larvae. In addition, immunized Xid mice did not generate parasite-specific immunoglobulin (Ig)M but did develop a weak IgG response compared to wild-type mice. These results demonstrate a dichotomy in the requirement of B cells in immunity to S. stercoralis. B cells are not required in the primary response, yet they are required in the secondary immune response. B-1 cells are required for the secondary immune response and their role appears to be the production of IgM and not as a source of immunoregulatory molecules.

Animals↗
PubMed2001

Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin.

Asthma and helminth infections induce similar immune responses characterized by the presence of peripheral blood eosinophilia and elevated serum IgE levels. Epidemiological surveys have reported either increases or decreases in the development of atopic diseases and asthma based on the prevalence of helminth infections in the population. The aim of this study was to determine if a pre-existing helminth infection would increase or decrease subsequent allergic responses to an unrelated allergen in the lungs. BALB/cByJ mice were infected with the nematode parasite Strongyloides stercoralis prior to ovalbumin (OVA) immunization and intratracheal challenge. Bronchoalveolar lavage (BAL) and fluid (BALF) were collected 3 days post-challenge and cellular and humoral immune responses were measured. Intracellular cytokine staining revealed increased IL-4 and IL-5 producing cells in BAL from mice infected with S. stercoralis before OVA sensitization. Increased IL-5 protein levels and decreased IFN-gamma protein levels were also observed in the BALF. There was, however, no increase in airway eosinophil accumulation in mice infectd with parasites before sensitization with OVA as compared to mice exposed to OVA alone. Furthermore, eotaxin levels in the lungs induced by OVA was suppressed in mice infected with the parasite before OVA sensitization. The development of OVA specific IgE responses in BALF was also impaired in mice infected with the parasite before sensitization with OVA. These results suggest that a pre-existing helminth infection may potentiate a systemic Type 2-type response yet simultaneously suppress in the lungs allergen-specific IgE responses and eotaxin levels in response to subsequent exposure to allergens.

Allergens↗
PubMed2003

Predictive markers for development of strongyloidiasis in patients infected with both Strongyloides stercoralis and HTLV-1.

Severe strongyloidiasis has often been reported to occur in some patients infected with both Strongyloides stercoralis (S. stercoralis) and human T-cell leukaemia virus type 1 (HTLV-1); however, there are few useful predictive markers for the risk of development of strongyloidiasis in these patients. To search for such predictive markers, we examined peripheral blood and stool samples of individuals infected with both S. stercoralis and HTLV-1 in Okinawa, Japan, an area in which both of these are endemic. The HTLV-1 proviral load and antibody titre were examined in relation to the S. stercoralis load as measured by the direct faecal smear method in patients infected with both S. stercoralis and HTLV-1. The Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) antibody titre was also measured in these patients in order to examine the relationship between host immunity and HTLV-1 proviral load or antibody titre. The direct faecal smear-positive group showed both a higher HTLV-1 proviral load and HTLV-1 antibody titre than the -negative group (P < 0.05). In contrast, inverse correlations of these parameters with the EBNA antibody titre were observed, especially for proviral load (rho = -0.387, P < 0.05). These results suggest that HTLV-1 proviral load and antibody titre influence the S. stercoralis load via disturbance of the host immunity, and that proviral load would be an especially useful predictive marker of the risk of development of strongyloidiasis in patients infected with both S. stercoralis and HTLV-1.

Adult↗
PubMed1998

Regulation of primary Strongyloides ratti infections in mice: a role for interleukin-5.

C57BL/6 mice genetically deficient in interleukin-5 (IL-5-/-) and normal C57BL/6 (IL-5+/+) mice were infected with larvae of a homogonic strain of the nematode Strongyloides ratti. In primary infections both male and female IL-5-/- mice released two to four times more eggs and larvae than IL-5+/+ mice. IL-5-/- mice harboured about 60% more intestinal worms, which were more fecund, than IL-5+/+ mice. The duration of the infection was similar in normal and IL-5-deficient mice. Both IL-5-/- and IL-5+/+ mice resisted a secondary infection. IL5-/- mice lost more weight during the infection than normal mice and took longer to regain their initial weight after expelling the worms. The number of eosinophils increased in the bone marrow, peritoneal cavity and small intestine of IL-5+/+ mice, but not IL-5-/- mice, following infection. No significant differences between infected IL-5+/+ and IL-5-/- mice in mast cells or other leucocytes were observed in the peritoneal cavity. Thus, IL-5 functions to protect the host in a primary infection of S. ratti by limiting the number and fecundity of worms establishing in the small intestine. This protection is correlated with elevated blood and tissue eosinophilia which occurs in normal mice but not in IL-5-/- mice.

Animals↗