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Nerve remodelling during intestinal inflammation.

The intestinal mucosa contains a dense nerve network and many inflammatory cells, and these may interact through the exchange of regulatory molecules. Evidence suggests that intestinal mucosal mast cells are innervated, and it is known that the density of this cell type changes significantly in nematode-infected rats. Recent data indicates that rat jejunal mucosal nerves remodel after Nippostrongylus brasiliensis infection, with degenerative and regenerative phases during the acute and recovery stages of inflammation. Seven weeks postinfection there is a net increase in the density and number per villus of mucosal nerves. These changes suggest that mucosal nerves exhibit structural plasticity in inflamed tissues, which must impact on interactions between the enteric nervous system and other mucosal elements in disease.

Animals↗

Generation and analysis of interleukin-4 deficient mice.

Interleukin-4 (IL-4) promotes the growth and differentiation of many hematopoietic cells in vitro; in particular, it directs the immunoglobulin (Ig) class switch to IgG1 and IgE. Mice homozygous for a mutation that inactivates the IL-4 gene were generated to test the requirement for IL-4 in vivo. In the mutant mice T and B cell development was normal, but the serum levels of IgG1 and IgE were strongly reduced. The IgG1 dominance in a T cell-dependent immune response was lost, and IgE was not detectable upon nematode infection. Thus, some but not all of the in vitro properties of IL-4 are critical for the physiology of the immune system in vivo.

Aging↗

Calgranulin C has filariacidal and filariastatic activity.

The calgranulins are a family of calcium- and zinc-binding proteins produced by neutrophils, monocytes, and other cells. Calgranulins are released during inflammatory responses and have antimicrobial activity. Recently, one of the calgranulins, human calgranulin C (CaGC), has been implicated as an important component of the host responses that limit the parasite burden during filarial nematode infections. The goal of this work was to test the hypothesis that human CaGC has biologic activity against filarial parasites. Brugia malayi microfilariae and adults were exposed in vitro to 0.75 to 100 nM recombinant human CaGC. Recombinant CaGC affected adult and larval parasites in a dose-dependent fashion. Microfilariae were more sensitive to the action of CaGC than were adult parasites. At high levels, CaGC was both macrofilariacidal and microfilariacidal. At lower levels, the percentage of parasites killed was dependent on the level of CaGC in the culture system. The larvae not killed had limited motility. The filariastatic effect of low-level CaGC was reversed when the CaGC was removed from the culture system. Immunohistochemical analysis demonstrated that human CaGC accumulated in the cells of the hypodermis-lateral chord of adult and larval parasites. The antifilarial activity of CaGC was not due to the sequestration of zinc. Thus, the cellular and molecular mechanisms that result in the production and release of CaGC in humans may play a key role in the regulation of filarial parasite numbers.

Animals↗

The evolution of adaptive immunity.

Approximately 500 mya two types of recombinatorial adaptive immune systems appeared in vertebrates. Jawed vertebrates generate a diverse repertoire of B and T cell antigen receptors through the rearrangement of immunoglobulin V, D, and J gene fragments, whereas jawless fish assemble their variable lymphocyte receptors through recombinatorial usage of leucine-rich repeat (LRR) modular units. Invariant germ line-encoded, LRR-containing proteins are pivotal mediators of microbial recognition throughout the plant and animal kingdoms. Whereas the genomes of plants and deuterostome and chordate invertebrates harbor large arsenals of recognition receptors primarily encoding LRR-containing proteins, relatively few innate pattern recognition receptors suffice for survival of pathogen-infected nematodes, insects, and vertebrates. The appearance of a lymphocyte-based recombinatorial system of anticipatory immunity in the vertebrates may have been driven by a need to facilitate developmental and morphological plasticity in addition to the advantage conferred by the ability to recognize a larger portion of the antigenic world.

Adaptation, Physiological↗

Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells.

T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which activate signal transducer and activator of transcription 6 (STAT6) are expressed in the muscularis externa during nematode infection and are candidate mediators of the associated hypercontractility. To determine the locus of action of these cytokines, we examined the IL-4- and IL-13-induced hypercontractility of the isolated muscle cells from STAT6 +/+ and STAT6 -/- mice. We compared the results with cells isolated from Trichinella spiralis-infected STAT6 +/+ and STAT6 -/- mice. Carbamylcholine chloride (Carbachol) induced the contraction of jejunal muscle cells in a concentration-dependent manner maximal contraction (R(max) 26.7 +/- 1.9%). Cells from T. spiralis-infected STAT6 -/- mice showed the hypertrophy (cell lengths 41.4 +/- 0.8 to 89.0 +/- 8.7 microm) and hypercontractility (R(max) 37.5 +/- 1.3%) induced by infection. IL-4Ralpha mRNA was detected in dispersed smooth muscle cells. Incubation of longitudinal muscle-myenteric plexus (LMMP) with IL-4 and IL-13 enhanced Carbachol-induced muscle contraction (R(max) 35.5 +/- 1.9 and 32.4 +/- 2.9%, respectively). Incubation of LMMP from STAT6 -/- mice with IL-4 did not enhance the contraction. The hypercontractility in T. spiralis-infected mice was attenuated in STAT6 -/- mice (P < 0.02). These results indicate both IL-4 and IL-13 induce hypercontractility of muscle cells via the STAT6 pathway, and this is the basis for hypercontractility observed in T. spiralis-infected mice.

Animals↗

Toxocara-induced eosinophilic inflammation. Airway function and effect of anti-IL-5.

The immunoinflammatory response to parasitic nematode infections and allergic diseases have some similarities, the most profound being the increases in eosinophils and serum total IgE concentration. Whether parasitic infections stimulate or inhibit allergic asthma is a matter of debate. We investigated the effect of Toxocara canis (T. canis) infection on airway function in BALB/c mice at various days post-infection. Within 24 h after infection, the trachea responded hyperreactive to carbachol stimulation. Eosinophils, and to a lesser degree lymphocytes, infiltrated the airways causing interstitial and alveolar inflammation (7 d post-infection). Concurrently with cell infiltration, the trachea became hyporesponsive to carbachol whereas the pulmonary resistance was increased and the dynamic compliance decreased. The hyporeactive response could be simulated in vitro by incubating normal tracheae with eosinophil-enriched bronchoalveolar lavage cells obtained from infected mice. The response depended on the number of cells added to the medium, a lower number causing a hyper- and a higher number a hyporeactive response. Anti-interleukin-5 (anti-IL-5) producing hybridoma cells given simultaneously with T. canis infection inhibited eosinophil infiltration in the airways but not that of lymphocytes. Anti-IL-5 treatment prevented tracheal hyporeactivity but not perivascular and peribronchial edema, increased pulmonary resistance, or decreased dynamic compliance. Treatment with isotype control antibody did not affect eosinophil number nor the observed changes in airway functions. It was concluded that T. canis-induced airway inflammation coincided with increased pulmonary resistance, decreased dynamic compliance, and perivascular/peribronchial edema. These phenomena were independent on the presence of eosinophils, whereas tracheal hyporeactivity was clearly associated with airway eosinophilia.

Animals↗

Redescription of Pterygodermatites (Mesopectines) nycticebi (Mönnig, 1920) (Nematoda: Rictulariidae), a parasite of slow loris Nycticebus coucang (Mammalia: Primates).

Pterygodermaties (Mesopectines) nycticebi (Mönnig, 1920) (Nematoda: Spirurida: Rictulariidae) is redescribed based on immature and mature adults collected from the stomach and small intestine at autopsy of a slow loris, Nycticebus coucang (Boddaert, 1785) (Mammalia: Primates), in a zoological garden in Japan. It is first demonstrated that male possesses a minute telamon and a left lateral pore in the preanal part of body. The cause of death of the slow loris is strongly surmised to be related to the nematode infection, which was apparently acquired under captivity in the zoological garden.

Animals↗

[Selective vs. mass treatment with antihelminthic drugs: experience in two hyperendemic communities].

OBJECTIVE: To compare the prevalence and intensity of soil-transmitted nematode infection among children from two hyperendemic communities who were treated with antihelminthic drugs under two different regimens: selective or individual treatment was administered to members of one of the communities, and repeated mass treatment was given to the control community. METHODS: The study population was comprised of 909 children of both sexes between the ages of 2 and 13 from two peri-urban communities: Las Lomas and El Abastos, both in Santa Fe, Argentina. A prospective, longitudinal, quasi-experimental study was carried out in these communities. During the 22-month study period, 5 parasitologic controls were performed and results were qualitatively and quantitatively examined. Treatment with antihelminthic drugs was given at controls 0, 2, 3, and 4. At Las Lomas, selective treatment was administered to those in sample A (n = 55) who were positive for parasites; in El Abasto, mass treatment was given to all children, including those in sample B (n = 50). Both samples received follow-up. RESULTS: The prevalence and intensity of A. lumbricoides infections were found to be significant in El Abasto. No differences were detected in the case of T. trichiura. When prevalence and parasitic burden of A. lumbricoides were compared among controls within a single community (at the beginning and end of the study), no significant differences were observed in sample A, but a significant difference was seen in sample B. Insofar as T. trichiura is concerned, there were significant differences among controls in both samples. CONCLUSIONS: Only repeated and massive treatment significantly lowered the prevalence and intensity of A. lumbricoides infections during the study period.

Adolescent↗

Anthelmintic and nutritional effects of heather supplementation on Cashmere goats grazing perennial ryegrass-white clover pastures.

To investigate anthelmintic and nutritional effects of heather supplementation in goats grazing perennial ryegrass-white clover pastures, 40 dry Cashmere goats were randomly assigned to 4 treatments in a 2 x 2 factorial arrangement: 2 grazing management treatments (supplementation with heather vs. nonsupplementation) and 2 anthelmintic treatments (treatment vs. nontreatment). Goats grazed continuously from May to September 2004. At the end of the grazing period, the number of dead goats due to gastrointestinal parasitism was 1 in the group supplemented with heather and dosed with anthelmintic, 4 in the group that received neither supplementation nor anthelmintic, and 0 in the other 2 groups. For goats that did not receive anthelmintic treatment, the percentage of heather in the diet was negatively correlated with fecal egg count in August (r = -0.59, P < 0.05) and September (r = -0.49, P < 0.1) and positively correlated (r = 0.54, P < 0.05) with BW changes during the grazing season. Therefore, the correlation coefficient between BW change and fecal egg count was negative (r = -0.62, P < 0.05). Rumen ammonia concentrations were always lower in supplemented goats (P < 0.05). However, VFA concentrations were greater in goats consuming heather (58.9 vs. 50.9 mmol/L), which suggests that ruminal fermentation was not adversely affected by consumption of tannins. Heather availability in the vegetation might represent a valuable opportunity and sustainable method to control gastrointestinal nematode infections in a goat production system based on grazing perennial ryegrass-white clover pastures.

Ammonia↗

Larvae of Contracaecum sp. among inshore fish species of southwestern Australia.

Larval nematode infections were investigated in 236 fish from 17 estuarine and near-shore species in southwestern Australia. Larvae of the genus Contracaecum were found in 4 species of fish (Acanthopagrus butcheri, Sillaginodes punctata, Mugil cephalus and Aldrichetta forsteri). The prevalence and intensity of infection was highest in the 2 species of mullet: 81% infected and 9.8 +/- 1.5 larvae fish(-1) for M. cephalus; 100% and 12.7 +/- 3.7 larvae fish(-1) for A. forsteri. There was no evidence of post-mortem migration of worms from the visceral organs to the musculature of the fish.

Animals↗

Modulation of macrophage cytokine production by ES-62, a secreted product of the filarial nematode Acanthocheilonema viteae.

Parasite survival and host health may depend on the ability of the parasite to modulate the host immune response by the release of immunomodulatory molecules. Excretory-secretory (ES)-62, one such well-defined molecule, is a major secreted protein of the rodent filarial nematode Acanthocheilonema viteae, and has homologues in human filarial nematodes. Previously we have shown that ES-62 is exclusively associated with a Th2 Ab response in mice. Here we provide a rationale for this polarized immune response by showing that the parasite molecule suppresses the IFN-gamma/LPS-induced production, by macrophages, of bioactive IL-12 (p70), a key cytokine in the development of Th1 responses. This suppression of the induction of a component of the host immune response extends to the production of the proinflammatory cytokines IL-6 and TNF-alpha, but not NO. The molecular mechanism underlying these findings awaits elucidation but, intriguingly, the initial response of macrophages to ES-62 is to demonstrate a low and transient release of these cytokines before becoming refractory to further release induced by IFN-gamma/LPS. The relevance of our observations is underscored by the finding that macrophages recovered from mice exposed to "physiological" levels of ES-62 by the novel approach of continuous release from implanted osmotic pumps in vivo were similarly refractory to release of IL-12, TNF-alpha, IL-6, but not NO, ex vivo. Therefore, our results suggest that exposure to ES-62 renders macrophages subsequently unable to produce Th1/proinflammatory cytokines. This likely contributes to the generation of immune responses with an anti-inflammatory Th2 phenotype, a well-documented feature of filarial nematode infection.

Adjuvants, Immunologic↗