Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice

Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less-developed countries. Helminths, common in less-developed countries, may induce immunoregulatory circuits protective against IBD. IL-10(-/-) mice given piroxicam develop severe and persistent colitis. Lamina propria mononuclear cells from colitic IL-10(-/-) mice released IFN-gamma and IL-12. The ongoing piroxicam-induced colitis could be partially blocked with anti-IL-12 monoclonal antibody suggesting that the inflammation was at least partly IL-12 dependent. Colonization of piroxicam-treated colitic IL-10(-/-) mice with Heligmosomoides polygyrus (an intestinal helminth) suppressed established inflammation and inhibited mucosal IL-12 and IFN-gamma production. H. polygyrus augmented mucosal IL-13, but not IL-4 or IL-5 production. Transfer of mesenteric lymph node (MLN) T cells from IL-10(-/-) animals harboring H. polygyrus into colitic IL-10(-/-) recipients inhibited colitis. MLN T cells from worm-free mice did not. Foxp3 (scurfin) drives regulatory T cell function. H. polygyrus enhanced Foxp3 mRNA expression in MLN T cells that had regulatory activity. This suggests that H. polygyrus inhibits ongoing IL-10(-/-) colitis in part through blocking mucosal Th1 cytokine production. Resolution of inflammation is associated with increased IL-13 production and can be adoptively transferred by MLN T cells.     

IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis

The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2 cytokine production and eosinophilia. The scope of the present study was to directly elucidate the role of interleukin-5 (IL-5) and eosinophils in controlling the development of L. sigmodontis after vaccination and in primary infection. BALB/c mice immunized with irradiated third-stage larvae (L3) were confirmed to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppressed both blood and tissue eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive filarial infection, that IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected mice, anti-IL-5 treatment did not modify filarial infection within the 1st month, most likely because during primary infection IL-5-dependent mechanisms such as subcutaneous eosinophilia are induced too late to disturb worm establishment. However, there is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsulation is also under the control of IL-5. Received: 30 March 2000     

Inefficient and abortive classical complement pathway activation by the calcium inositol hexakisphosphate component of the Echinococcus granulosus laminated layer

Persistent extracellular tissue-dwelling pathogens face the challenge of antibody-dependent activation of the classical complement pathway (CCP). A prime example of this situation is the larva of the cestode Echinococcus granulosus sensu lato, causing cystic echinococcosis. This tissue-dwelling, bladder-like larva is bounded by a cellular layer protected by the outermost acellular “laminated layer” (LL), to which host antibodies bind. The LL is made up of a mucin meshwork and interspersed nano-deposits of calcium inositol hexakisphosphate (calcium InsP₆). We previously reported that calcium InsP₆ bound C1q, apparently initiating CCP activation. The present work dissects CCP activation on the LL. Most of the C1 binding activity in the LL corresponded to calcium InsP₆, and this binding was enhanced by partial proteolysis of the mucin meshwork. The remaining C1 binding activity was attributable to host antibodies, which included CCP-activating IgG isotypes. Calcium InsP₆ made only a weak contribution to early CCP activation on the LL, suggesting inefficient C1 complex activation as reported for other polyanions. CCP activation on calcium InsP₆ gave rise to a dominant population of C3b deposited onto calcium InsP₆ itself that appeared to be quickly inactivated. Apparently as a result of inefficient initiation plus C3b inactivation, calcium InsP₆ made no net contribution to C5 activation. We propose that the LL protects the underlying parasite cells from CCP activation through the combined effects of inefficient permeation of C1 through the mucins and C1 retention on calcium InsP₆. This mechanism does not result in C5 activation, which is known to drive parasite-damaging inflammation.     

Use of dried blood spots to define antibody response to the Strongyloides stercoralis recombinant antigen NIE

An approach to improve the diagnosis of Strongyloides stercoralis infection is the use of serologic assays utilising the NIE antigen from S. stercoralis, with good diagnostic sensitivity and excellent specificity reported. Detection of antibody eluted from dried blood spots (DBS) has shown utility in large-scale seroepidemiological studies for a range of conditions and is appealing for use with children where sample collection is difficult. We adapted an existing NIE-enzyme linked immunosorbent assay (ELISA) for the testing of strongyloides antibody response on DBS, and evaluated it in a population screening and mass drug administration programme (MDA) for strongyloidiasis conducted in an Australian indigenous community. Study participants were treated with 200 μg/kg ivermectin (>15 kg) or 3× 400 mg albendazole (<15 kg). The sensitivity of the NIE DBS-ELISA was determined by receiver operator characteristic (ROC) analysis to be 85.7%. A total of 214 DBS were collected from 184 participants across two screening and MDA encounters. A total of 27 of 164 participants (16.5%) tested positive for S. stercoralis NIE-DBS prior to MDA treatment, and 6 of 50 participants (12.0%) tested positive after treatment. These prevalence values are similar to those documented by standard serology in the same community. For 30 participants where a DBS was collected at both MDA 1 and 2, a significant decline in ELISA values was evident post treatment (0.12–0.02, p = 0.0012). These results are in agreement with previous studies documenting the high seroprevalence of S. stercoralis in remote Australian Indigenous communities, and suggest that collection of dried blood spots may be a useful approach for field diagnosis of S. stercoralis seroprevalence.     

白细胞介素-15抗寄生虫感染的研究进展

白细胞介素-15(IL-15)是一种可溶性细胞因子,作为多种免疫细胞的趋化因子参与并调节机体炎症反应及免疫反应。目前,IL-15的分子结构与受体得到广泛研究,其信号转导方式也取得了较大进展,然而其在寄生虫学上的研究起步较晚。本文对近年来IL-15在抗蠕虫及原虫感染等方面的最新研究进展作一综述,并对其免疫增强作用机制和应用前景进行了展望,为进一步探索IL-15抗寄生虫免疫作用及其在寄生虫学的相关应用研究提供参考。     

常见蠕虫感染Th17细胞及IL-17细胞因子作用研究新进展

蠕虫感染在我国广泛流行,现阶段感染率有上升的趋势。蠕虫感染通过各种抗原及分泌物刺激机体产生免疫反应。Th17细胞是新发现的CD4+T细胞的亚群,其主要分泌IL-17。IL-17具有广泛的生物学效应,介导多种炎症因子及激活免疫反应。在蠕虫感染中,Th17及IL-17对宿主清除寄生虫及介导免疫病理反应起到了重要作用。本文综述了Th17及IL-17的调节机制及在常见蠕虫感染中Th17及IL-17的作用机制。     

Nematode infection: A rare mimic of acute appendicitis

INTRODUCTION

Acute appendicitis is a common condition seen in all surgical units. One rare condition that can mimic acute appendicitis is a nematode infection of the bowel. There have been few reported cases of nematode infection within the appendix and none that have been accompanied by intra-operative pictures.

PRESENTATION OF CASE

A 16-year-old female presented with a 12 h history of right iliac fossa pain and mild pyrexia. Bloods showed a neutrophilia and normal C-reactive protein. Laparoscopy was performed which revealed a non-inflamed appendix. The appendix was dissected and a live nematode was visualised exiting the base of the appendix. Anti-helminthics were given and the infection resolved.

DISCUSSION

Nematode infection is most commonly seen in Africa, Asia and South America. When seen within the United Kingdom (UK), it is seen most commonly within high-risk populations. Testing for these infections is not routine within the UK and when they are performed, the results take a considerable amount of time to return. These tests should be considered within high-risk populations so that unnecessary surgery can be avoided.

CONCLUSION

This case highlights the importance of considering rare causes of right iliac fossa pain including nematode infection in a young patient. The case highlights this by giving intra-operative pictures of live nematodes upon dissection of the appendix.     

Multifocal hydatid disease in a child

One of the most serious helminth infections in humans with widespread occurrence is hydatid disease. Although the majority of the cases are referred in adults, many of them have to do with children. The hydatid cysts can occur in any organ of the human body and in rare cases in a combination of different sites. We present the case of a young boy with hydatid cysts in both lungs and in the upper pole of the left kidney. The rarity of this case is the unusual combination of the cyst development in these organs without the involvement of the liver.     

Accuracy of the Kato-Katz, adhesive tape and FLOTAC techniques for helminth diagnosis among children in Kyrgyzstan

The purpose of this study was to assess the accuracy of three copro-microscopic techniques for helminth diagnosis: Kato-Katz, adhesive tape and FLOTAC. A total of 163 children from a peri-urban municipality near Bishkek, Kyrgyzstan, participated and submitted multiple stool samples and adhesive tapes. Ninety children supplied at least two stool samples and two adhesive tapes. Three stool samples and three adhesive tapes were available from 71 and 64 children, respectively. From each stool sample, a single Kato-Katz thick smear was prepared and examined quantitatively. Additionally, the first stool sample was subjected to the FLOTAC technique and helminth eggs were counted. Adhesive tapes were checked for the presence of Enterobius vermicularis eggs. Using pooled results as a diagnostic ‘gold’ standard, the prevalence of Ascaris lumbricoides, E. vermicularis, Hymenolepis nana and Dicrocoelium dendriticum were 54.4%, 13.3%, 11.1% and 11.1%, respectively. Infection intensities were low. When compared to triplicate Kato-Katz, a single FLOTAC was more sensitive for the diagnosis of A. lumbricoides (89.5% versus 39.5%) and D. dendriticum (88.9% versus 33.3%), but less sensitive for H. nana (66.7% versus 88.9%). For E. vermicularis, three adhesive tapes showed much higher sensitivity than a single FLOTAC (92.9% versus 14.3%). FLOTAC yielded significantly higher faecal egg counts than Kato-Katz for A. lumbricoides and D. dendriticum. Overall results suggest that, although FLOTAC represents a promising technique for helminth diagnosis in Kyrgyzstan, the repeated adhesive tape test remains so far the method of choice for diagnosing E. vermicularis.