Interleukin-33 Induces the Enzyme Tryptophan Hydroxylase 1 to Promote Inflammatory Group 2 Innate Lymphoid Cell-Mediated Immunity.

Group 2 innate lymphoid cells (ILC2s) regulate immunity, inflammation, and tissue homeostasis. Two distinct subsets of ILC2s have been described: steady-state natural ILC2s and inflammatory ILC2s, which are elicited following helminth infection. However, how tissue-specific cues regulate these two subsets of ILC2s and their effector functions remains elusive. Here, we report that interleukin-33 (IL-33) promotes the generation of inflammatory ILC2s (ILC2INFLAM) via induction of the enzyme tryptophan hydroxylase 1 (Tph1). Tph1 expression was upregulated in ILC2s upon activation with IL-33 or following helminth infection in an IL-33-dependent manner. Conditional deletion of Tph1 in lymphocytes resulted in selective impairment of ILC2INFLAM responses and increased susceptibility to helminth infection. Further, RNA sequencing analysis revealed altered gene expression in Tph1 deficient ILC2s including inducible T cell co-stimulator (Icos). Collectively, these data reveal a previously unrecognized function for IL-33, Tph1, and ICOS in promoting inflammatory ILC2 responses and type 2 immunity at mucosal barriers.

Body Protein Reserves Sustain Maternal Performance in Early Lactation but Dietary Protein Is Necessary to Maintain Performance and Immune Responses to Nippostrongylus brasiliensis in Lactating Rats.

Background: It has been shown that dietary protein supplementation during lactation boosts immunity in Nippostrongylus brasiliensis-infected periparturient rats. It is not known whether body protein reserves accumulated during gestation have a similar effect during lactation. Objective: This study aimed to quantify the impact of body protein reserves and dietary protein supplementation on maternal performance and immune responses to N. brasiliensis during lactation. Methods: Multiparous female Sprague-Dawley rats were administered a primary infection of N. brasiliensis before mating and were restriction-fed either 60 g [low-protein diet gestation (Lge)] or 210 g [high-protein diet gestation (Hge)] crude protein (CP) per kilogram of dry matter (DM) until parturition. From parturition onward, dams were restriction-fed either 100 g [low-protein diet lactation (Lla)] or 300 g [high-protein diet lactation (Hla)] CP per kilogram of DM, generating 4 different dietary treatments. A subset of rats was sampled before parturition; postparturition, dams were secondarily infected with N. brasiliensis and samples were collected at days 5 and 11 postparturition. Results: Maternal performance until parturition, as measured by pup weight, was better in Hge rats than in Lge rats [Lge: 4.84 g; Hge: 6.15 g; standard error of the difference (SED): 0.19]. On day 11, pup weights of dams with reduced protein reserves fed protein during lactation (Lge-Hla; 20.28 g) were higher than their counterparts from Hge-Lla dams (17.88 g; SED: 0.92). Worm counts were significantly different between Lge-Lla-fed (253; 95% CI: 124, 382) and Hge-Hla-fed (87; 95% CI: 22, 104) dams on day 11 (P = 0.024). The expression of splenic interleukin 13 (Il13) and arachidonate 15-lipoxygenase (Alox15) was significantly higher (P < 0.05) in Hge-Hla dams compared with Lge-Lla dams on day 5. Conclusions: Although protein reserves were adequate to maintain maternal performance in the early stage of lactation in dams infected with N. brasiliensis, they were not adequate to maintain maternal performance and effective immune responses at later stages. Dietary protein supplementation was required to achieve this.

Host- and Helminth-Derived Endocannabinoids That Have Effects on Host Immunity Are Generated during Infection.

Helminths have coevolved with their hosts, resulting in the development of specialized host immune mechanisms and parasite-specific regulatory products. Identification of new pathways that regulate helminth infection could provide a better understanding of host-helminth interaction and may identify new therapeutic targets for helminth infection. Here we identify the endocannabinoid system as a new mechanism that influences host immunity to helminths. Endocannabinoids are lipid-derived signaling molecules that control important physiologic processes, such as feeding behavior and metabolism. Following murine infection with Nippostrongylus brasiliensis, an intestinal nematode with a life cycle similar to that of hookworms, we observed increased levels of endocannabinoids (2-arachidonoylglycerol [2-AG] or anandamide [AEA]) and the endocannabinoid-like molecule oleoylethanolamine (OEA) in infected lung and intestine. To investigate endocannabinoid function in helminth infection, we employed pharmacological inhibitors of cannabinoid subtype receptors 1 and 2 (CB1R and CB2R). Compared to findings for vehicle-treated mice, inhibition of CB1R but not CB2R resulted in increased N. brasiliensis worm burden and egg output, associated with significantly decreased expression of the T helper type 2 cytokine interleukin 5 (IL-5) in intestinal tissue and splenocyte cultures. Strikingly, bioinformatic analysis of genomic and transcriptome sequencing (RNA-seq) data sets identified putative genes encoding endocannabinoid biosynthetic and degradative enzymes in many parasitic nematodes. To test the novel hypothesis that helminth parasites produce their own endocannabinoids, we measured endocannabinoid levels in N. brasiliensis by mass spectrometry and quantitative PCR and found that N. brasiliensis parasites produced endocannabinoids, especially at the infectious larval stage. To our knowledge, this is the first report of helminth- and host-derived endocannabinoids that promote host immune responses and reduce parasite burden.

A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development.

As part of on-going efforts to control hookworm infection, the "human hookworm vaccine initiative" has recognised blood feeding as a feasible therapeutic target for inducing immunity against hookworm infection. To this end, molecular approaches have been used to identify candidate targets, such as Necator americanus (Na) haemoglobinase aspartic protease-1 (APR-1), with immunogenicity profiled in canine and hamster models. We sought to accelerate the immune analysis of these identified therapeutic targets by developing an appropriate mouse model. Here we demonstrate that Nippostrongylus brasiliensis (Nb), a phylogenetically distant strongylid nematode of rodents, begins blood feeding early in its development and that immunisation with Na-APR-1 can block its growth and completion of its life cycle. Furthermore, we identify a new haem detoxification pathway in Nb required for blood feeding that can be blocked by drugs of the quinolone family, reducing both infection burden and the associated anaemia in rodents. Collectively, our findings show that haem metabolism has potential as a checkpoint for interrupting hookworm development in early stages of the hookworm life cycle and that the Nippostrongylus brasiliensis rodent model is relevant for identifying novel therapeutic targets against human hookworm.

IL-4 up-regulates cyclooxygenase-1 expression in macrophages.

Macrophages use various cell-surface receptors to sense their environment and undergo polarized responses. The cytokines, interleukin (IL)-4 and IL-13, released from T-helper type 2 (Th2) cells, drive macrophage polarization toward an alternatively activated phenotype (M2). This phenotype is associated with the expression of potent pro-resolving mediators, such as the prostaglandin (PG) D2-derived cyclopentenone metabolite, 15d-PGJ2, produced by the cyclooxygenase (Ptgs; Cox) pathway. Interestingly, IL-4 treatment of bone marrow-derived macrophages (BMDMs) significantly down-regulates Cox-2 protein expression, whereas Cox-1 levels are significantly increased. This phenomenon not only challenges the dogma that Cox-1 is only developmentally regulated, but also demonstrates a novel mechanism in which IL-4-dependent regulation of Cox-1 involves the activation of the mechanistic target of rapamycin complex (mTORC). Using specific chemical inhibitors, we demonstrate here that IL-4-dependent Cox-1 up-regulation occurs at the post-transcriptional level via the Fes-Akt-mTORC axis. Activation of AMP-activated protein kinase (AMPK) by metformin, inhibition of mTORC by torin 1, or CRISPR/Cas9-mediated genetic knock-out of tuberous sclerosis complex-2 (Tsc2) blocked the IL-4-dependent expression of Cox-1 and the ability of macrophages to polarize to M2. However, use of 15d-PGJ2 partially rescued the effects of AMPK activation, suggesting the importance of Cox-1 in macrophage polarization as also observed in a model of gastrointestinal helminth clearance. In summary, these findings suggest a new paradigm where IL-4-dependent up-regulation of Cox-1 expression may play a key role in tissue homeostasis and wound healing during Th2-mediated immune responses, such as parasitic infections.

Unusual terpenylated acylphloroglucinols from Dryopteris wallichiana.

Four unusual terpenylated acylphloroglucinols were isolated from the diethyl ether extract of the scales and rhizomes of the fern Dryopteris wallichiana together with the known compounds albaspidins AA and AB, and filixic acids ABA and ABB. Structures of the isolated compounds were established by extensive spectroscopic analysis and their absolute configuration at C-14″ was determined by comparing their CD spectra with those simulated for the respective isomers. Pure acylphloroglucinols displayed moderate in vitro nematocidal activity against L4 stage larvae of Nippostrongylus brasiliensis (LD50=22-121 µM).

Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice.

When animals are infected with helminthic parasites, resistant hosts show type II helper T immune responses to expel worms. Recently, natural helper (NH) cells or nuocytes, newly identified type II innate lymphoid cells, are shown to express ST2 (IL-33 receptor) and produce IL-5 and IL-13 when stimulated with IL-33. Here we show the relevant roles of endogenous IL-33 for Strongyloides venezuelensis infection-induced lung eosinophilic inflammation by using Il33(-/-) mice. Alveolar epithelial type II cells (ATII) express IL-33 in their nucleus. Infection with S. venezuelensis or intranasal administration of chitin increases in the number of ATII cells and the level of IL-33. S. venezuelensis infection induces pulmonary accumulation of NH cells, which, after being stimulated with IL-33, proliferate and produce IL-5 and IL-13. Furthermore, S. venezuelensis infected Rag2(-/-) mice increase the number of ATII cells, NH cells, and eosinophils and the expression of IL-33 in their lungs. Finally, IL-33-stimulated NH cells induce lung eosinophilic inflammation and might aid to expel infected worms in the lungs.

Hsp12.6 expression is inducible by host immunity in adult worms of the parasitic nematode Nippostrongylus brasiliensis.

Heat shock proteins (Hsp) are a family of stress-inducible molecular chaperones that play multiple roles in a wide variety of animals. However, the roles of Hsps in parasitic nematodes remain largely unknown. To elucidate the roles of Hsps in the survival and longevity of nematodes, particularly at the 2 most critical stages in their lifecycle, the infective-L3 stage and adult stage, which is subjected to host-derived immunological pressure, we examined the temporal gene transcription patterns of Hsp12.6, Hsp20, Hsp70, and Hsp90 throughout the developmental course of the nematode Nippostrongylus brasiliensis by reverse transcriptase real-time PCR. Nb-Hsp70 and Nb-Hsp90 expression were observed throughout the nematode's lifecycle, while the expression of Nb-Hsp20 was restricted to adults. Interestingly, Nb-Hsp12.6 showed a biphasic temporal expression pattern; i.e., it was expressed in infective-L3 larvae and in adults during worm expulsion from immunocompetent rats. However, the activation of Nb-Hsp12.6 in adult worms was aborted when they infected permissive athymic-rnu/rnu rats and was only marginal when they infected mast-cell-deficient Ws/Ws rats, which exhibited a low response of rat mast cell protease (RMCP) II and resistin-like molecule (Relm)-ß expression compared to those observed in immunocompetent rats. Moreover, the activation of Nb-Hsp12.6 was reversed when adult worms were transplanted into the naive rat intestine. These features of Nb-Hsp12.6, the expression of which is not only stage-specific in infective-L3, but is also inducible by mucosal immunity in adults, have implications for the survival strategies of parasitic nematodes in deleterious environmental conditions both outside and inside the host.

An atherogenic lipid profile with low serum paraoxonase-1 activity during nematode infection in rats.

BACKGROUND: Inflammation and oxidative stress are associated with cardiovascular diseases and underlying atherosclerosis. The high density lipoprotein (HDL)-associated paraoxonase-1 (PON1) enzyme is known to be involved in the protection of serum lipids from such oxidation. Nonetheless, the disturbances of lipid profile during nematode-infected model have not yet been studied. Therefore, we aimed to explore the effects of Nippostrongylus brasiliensis infection in male Wistar rats, a model of human gastrointestinal nematode infections, on hepatic PON1 synthesis and the levels of lipid parameters. MATERIALS AND METHODS: Nippostrongylus brasiliensis-infected rats fed standard and high-fat diets. Serum paraoxonase and arylesterase activities were measured on day 0, 2, 4, 7, and 14 post-infection (PI). Hepatic PONs and pro-inflammatory cytokines mRNA expression levels were evaluated in a standard diet-fed groups, and the disturbances in lipid profile as well as the levels of thiobarbituric acid reactive species (TBARS) and oxidized-LDL (Ox-LDL) were measured in high-fat diet-fed groups. RESULTS: We found that N. brasiliensis-infected rats fed the standard diet show a significant reduction in serum PON1 activity and down-regulation of hepatic PON1 mRNA expression as well as up-regulation of hepatic IL-1ß, IL-ß receptor (R), TNF-α, and TNFR1 mRNA expressions in association with hepatic recruitments of Kupffer cells and neutrohils. In the presence of the high-fat diet, N. brasiliensis infection increases serum triglycerides, total cholesterol, LDL/VLDL, TBARS and Ox-LDL as well as decreases serum HDL coinciding with a maximum serum PON1 reduction. CONCLUSIONS: Nippostrongylus brasiliensis infection can induce atherogenic lipid profile and reduce serum PON1 activity.

Activation of Nippostrongylus brasiliensis infective larvae is regulated by a pathway distinct from the hookworm Ancylostoma caninum.

Developmentally arrested infective larvae of strongylid nematodes are activated to resume growth by host-derived cues encountered during invasion of the mammalian host. Exposure of Nippostrongylus brasiliensis infective larvae to elevated temperature (37°C) is sufficient to activate signalling pathways which result in resumption of feeding and protein secretion. This occurs independently of exposure to serum or glutathione, in contrast to the hookworm Ancylostoma caninum, and is not initiated by chemical exsheathment. No qualitative differences in protein secretion were induced by host serum as visualised by two-dimensional SDS-PAGE, although exposure of larvae to an aqueous extract of rat skin did stimulate secretion of a small pre-synthesised bolus of proteins. Infective larvae began feeding after a lag period of 3-4 h at 37°C, reaching a maximum of 90% of the population feeding by 48 h. Neither a membrane permeant analogue of cyclic GMP nor muscarinic acetylcholine receptor agonists stimulated feeding at 20°C, and high concentrations of both compounds inhibited temperature-induced activation. LY294002, an inhibitor of phosphatidylinositol 3-kinase, Akt inhibitor IV, an inhibitor of Akt protein kinase, and ketoconazole, an inhibitor of cytochrome P450, all blocked resumption of feeding and protein secretion at 37°C. Serotonin increased the rate of feeding assessed by uptake of radiolabelled BSA, but could not initiate feeding independently of elevated temperature. Collectively, the data suggest that the early signalling events for larval activation in N. brasiliensis differ substantially from A. caninum, but that they may converge at pathways downstream of phosphatidylinositol 3-kinase involving steroid hormone synthesis.

B cells have distinct roles in host protection against different nematode parasites.

B cells can mediate protective responses against nematode parasites by supporting Th2 cell development and/or by producing Abs. To examine this, B cell-deficient mice were inoculated with Nippostrongylus brasiliensis or Heligmosomoides polygyrus. B cell-deficient and wild type mice showed similar elevations in Th2 cytokines and worm expulsion after N. brasiliensis inoculation. Worm expulsion was inhibited in H. polygyrus-inoculated B cell-deficient mice, although Th2 cytokine elevations in mucosal tissues were unaffected. Impaired larval migration and development was compromised as early as day 4 after H. polygyrus challenge, and administration of immune serum restored protective immunity in B cell-deficient mice, indicating a primary role for Ab. Immune serum even mediated protective effects when administered to naive mice prior to inoculation. This study suggests variability in the importance of B cells in mediating protection against intestinal nematode parasites, and it indicates an important role for Ab in resistance to tissue-dwelling parasites.

C-type lectins from the nematode parasites Heligmosomoides polygyrus and Nippostrongylus brasiliensis.

The C-type lectin superfamily is highly represented in all metazoan phyla so far studied. Many members of this superfamily are important in innate immune defences against infection, while others serve key developmental and structural roles. Within the superfamily, many proteins contain multiple canonical carbohydrate-recognition domains (CRDs), together with additional non-lectin domains. In this report, we have studied two gastrointestinal nematode parasites which are widely used in experimental rodent systems, Heligmosomoides polygyrus and Nippostrongylus brasiliensis. From cDNA libraries, we have isolated 3 new C-type lectins from these species; all are single-CRD proteins with short additional N-terminal domains. The predicted Hp-CTL-1 protein contains 156 aa, Nb-CTL-1 191 aa and Nb-CTL-2 183 aa; all encode predicted signal peptides, as well as key conserved sequence motifs characteristic of the CTL superfamily. These lectins are most similar to C. elegans CLEC-48, 49 and 50, as well as to the lectin domains of mammalian immune system proteins CD23 and CD206. RT-PCR showed that these H. polygyrus and N. brasiliensis genes are primarily expressed in the gut-dwelling adult stages, although Nb-CTL-2 transcripts are also prominent in the free-living infective larval (L3) stage. Polyclonal antibodies raised to Hp-CTL-1 and Nb-CTL-1 reacted to both proteins by ELISA, and in Western blot analysis recognised a 15-kDa band in secreted proteins of adult N. brasiliensis (NES) and a 19-kDa band in H. polygyrus ES (HES). Anti-CTL-1 antibody also bound strongly to the cuticle of adult H. polygyrus. Hence, live parasites release C-type lectins homologous to some key receptors of the mammalian host immune system, raising the possibility that these products interfere in some manner with immunological recognition or effector function.

The effect of infection history on the fitness of the gastrointestinal nematode Strongyloides ratti.

SUMMARY: Hosts in nature will often acquire infections by different helminth species over their lifetime. This presents the potential for new infections to be affected (particularly via the host immune response) by a host's history of previous con- or hetero-specific infection. Here we have used an experimental rat model to investigate the consequences of a history of primary infection with either Nippostrongylus brasiliensis, Strongyloides venezuelensis or S. ratti on the fitness of, and immunological response to, secondary infections of S. ratti. We found that a history of con-specific, but not hetero-specific, infection reduced the survivorship of S. ratti; the fecundity of S. ratti was not affected by a history of either con- or hetero-specific infections. We also found that a history of con-specific infection promoted Th2-type responses, as shown by increased concentrations of total IgE, S. ratti-specific IgG1, rat mast cell protease II (RMCPII), IL4 (but decreased concentrations of IFNgamma) produced by mesenteric lymph node cells in response to S. ratti antigen. Additionally, S. ratti-specific IgG1 was positively related to the intensity of both primary and secondary infections of S. ratti. Hetero-specific primary infections were only observed to affect the concentration of total IgE and RMCPII. The overall conclusion of these experiments is that the major immunological effect acting against an infection is induced by the infection itself and that there is little effect of prior infections of the host.

Decreased serum paraoxonase-1 activity during intestinal nematode (Nippostrongylus brasiliensis) infection in rats.

Reduced paraoxonase-1 (PON1) activity has been observed in a number of pathological conditions; however, little is known about the effects of intestinal nematode infections, such as Nippostrongylus brasiliensis, on paraoxonase activity. We observed a significant reduction in serum paraoxonase and arylesterase activity after N. brasiliensis infection in Wistar rats from Day 6 until Day 12 post-infection (p.i.) for serum paraoxonase and from Day 3 until Day 24 p.i. for arylesterase. In addition, N. brasiliensis infection increased serum concentrations of pro-inflammatory cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha), with maximum concentrations observed on Day 9 p.i. These cytokines are known to inhibit the synthesis of hepatic PON1 mRNA. Thus, the observed reduction in PON1 activity during N. brasiliensis infection is likely associated with inflammatory reactions mounted against the parasites.

Morphological differentiation and function of the coelomocytes in the parasitic stages of Nippostrongylus brasiliensis.

Female and male worms of Nippostrongylus brasiliensis exhibited sexual dimorphism based on the number of coelomocytes present. A surprising multiplicity of diverse morphological types of coelomocytes developed in both female and male worms during the parasitic cycle. Cytoplasmic processes began to appear on the surface membrane of coelomocytes in the late third-stage larvae (L3s) in the lungs, and they increased greatly in type, size, and morphology during the fourth and fifth stages. These structures were characterized primarily as complex filopodia, pseudopodia, and cytoplasmic pearls, which resulted in the formation of highly pleomorphic cells. Pearls, starting as small protuberances, progressively increased in size and number with larval growth and development. In the adult worms, a novel process of autocannibalism was initiated in many of the very large coelomocytes. The pearls grew enormously in size at the expense of the cytoplasm, forming a peripheral garland in 1 plane surrounding a residual, small, flat, cytoplasmic core containing the nucleus. The underlying "strategy" was to increase the surface-to-volume ratio of these huge cells to overcome the restriction imposed by eutely; the coelomocytes do not undergo cell division. This morphological innovation makes possible a more efficient uptake of nutrients and exocytosis of waste matter. Vesicles (presumably lysosomes) in the coelomocytes of the infective L3 store an extraordinarily high concentration of vitamin B12 (cobalamin, Cbl). At present, the only physiological function that can be assigned to coelomocytes of N. brasiliensis is the uptake, concentration, and storage of Cbl in the free-living stages, with the subsequent release of the molecule from the vesicles in the early phase of parasitism. Thus, stored Cbl in the infective L3 is made available for biochemical processes during the critical period of larval growth and differentiation initiated in the lung. A model of a hypothetical coelomocyte is presented relative to the processing and use of Cbl. Based on many criteria, it is possible that functional differences exist between different morphological types of coelomocytes in the parasitic stages of N. brasiliensis and that future studies will have to address this matter.

Innate immune responses to lung-stage helminth infection induce alternatively activated alveolar macrophages.

While it is well established that infection with the rodent hookworm Nippostrongylus brasiliensis induces a strongly polarized Th2 immune response, little is known about the innate host-parasite interactions that lead to the development of this robust Th2 immunity. We exploited the transient pulmonary phase of N. brasiliensis development to study the innate immune responses induced by this helminth parasite in wild-type (WT) and severe-combined immune deficient (SCID) BALB/c mice. Histological analysis demonstrated that the cellular infiltrates caused by N. brasiliensis transit through the lungs were quickly resolved in WT mice but not in SCID mice. Microarray-based gene expression analysis demonstrated that there was a rapid induction of genes encoding molecules that participate in innate immunity and in repair/remodeling during days 2 to 4 postinfection in the lungs of WT and SCID mice. Of particular note was the rapid upregulation in both WT and SCID mice of the genes encoding YM1, FIZZ1, and Arg1, indicating a role for alternatively activated macrophages (AAMs) in pulmonary innate immunity. Immunohistochemistry revealed that nearly all alveolar macrophages became YM1-producing AAMs as early as day 2 postinfection. While the innate responses induced during the lung phase of N. brasiliensis infection were similar in complexity and magnitude in WT and SCID mice, only mice with functional T cells were capable of maintaining elevated levels of gene expression beyond the innate window of reactivity. The induction of alternatively activated alveolar macrophages could be important for dampening the level of inflammation in the lungs and contribute to the long-term decrease in pulmonary inflammation that has been associated with helminth infections.

Anthelmintic efficacy of extracts of Spigelia anthelmia Linn on experimental Nippostrongylus braziliensis in rats.

Spigelia anthelmia Linn is used as a herb and is a common annual weed of cultivation in open re-growths, on unused land in towns as well as on road sides. The plant can grow to approximately 30 cm in height. The aim of this study was to screen extracts of Spigelia anthelmia for their anthelmintic activity against an experimental Nippostrongylus braziliensis infection in rats. Acute oral toxicity occurred at a dose of 1,140 mg/kg, while anthelmintic trials against Nippostrongylus braziliensis in rats using the aqueous fraction showed a progressive decrease in worm count with increasing dose (10, 13, 16, 20 and 25 mg per kg body weight) (p < 0.05). At 25 mg per kg body weight, the worm count was significantly lower than that at 10 mg per kg body weight (p < 0.05).

Nematode infection in Alymphoplasia (aly) mice: worm species-dependent differential effect of defects of the gut-associated lymphatic tissue system.

Mice homologous for the alymphoplasia mutation (aly) show the systemic absence of secondary lymphoid tissues, with disorganized splenic architecture, including the absence of the germinal centre and follicular dendritic cells. In this study, we examined the influence of defects of gut-associated lymphoid tissue (GALT), such as Peyer's patches and the mesenteric lymph nodes, on the host response to helminth infection in aly/aly mice. The present study showed that most of the worms were expelled by day 7 after Nippostrongylus brasiliensis infection in both control aly/+ and aly/aly mice. In aly/aly mice, the number of peripheral blood eosinophils, intestinal goblet cells and mucosal mast cells were increased by N. brasiliensis infection in aly/aly mice to the same level as in the controls. Conversely, aly/aly mice developed more severe Heligmosomoides polygyrus infections than control aly/+ mice, as demonstrated by increased faecal egg counts, with reduced immune responses such as the numbers of intestinal goblet cells and mucosal mast cells. These results suggested that the dependency of GALT in activation of Th2 responses against gastrointestinal nematodes was different depending on the species of nematode.

Inhibition of neutrophil recruitment by ES of Nippostrongylus brasiliensis.

It has been reported that excretory-secretory (ES) material from the parasitic nematode Nippostrongylus brasiliensis has potential modulatory effects on the host's immune system. We observed that intratracheal instillation of ES from the L3 stage of the parasite reduced neutrophil numbers in LPS-induced inflammation as assessed by bronchoalveolar lavage.