| Home | E-Submission | Sitemap | Contact us |  
top_img
Korean J Parasitol > Volume 47(Suppl):2009 > Article
Shin, Lee, and Min: Eosinophil-Mediated Tissue Inflammatory Responses in Helminth Infection

Abstract

Eosinophilic leukocytes function in host protection against parasitic worms. In turn, helminthic parasites harbor specific molecules to evade or paralyze eosinophil-associated host immune responses; these molecules facilitate the migration and survival of parasitic helminths in vivo. This competition between eosinophil and worm leads to stable equilibria between them. An understanding of such dynamic host-eosinophil interactions will help us to uncover mechanisms of cross talk between host and parasite in helminth infection. In this review, we examine recent findings regarding the innate immune responses of eosinophils to helminthic parasites, and discuss the implications of these findings in terms of eosinophil-mediated tissue inflammation in helminth infection.

INTRODUCTION

Eosinophils, terminally differentiated granulocytic leukocytes that reside primarily in vertebrate mucosal tissues and function in host defense, are involved in the tissue pathogenesis caused by parasitic helminth infection [1]. During parasitic infections, the numbers of peripheral blood eosinophils are highly increased under the influence of Th2 cell-derived IL-5, IL-3 and GM-CSF, and eosinophils are recruited from the circulation into inflamed or damaged tissues by the eosinophil selective chemokine, eotaxin [2]. The recruited eosinophils are primed by interaction with connective tissue matrix proteins such as fibronectin and laminin before being activated by cytokines through receptor-mediated signals. The fully activated eosinophils then liberate histotoxic or helminthotoxic reactive oxygen species and granular proteins [3]. Besides these peripheral effector functions, eosinophils modulate immune responses by releasing cytokines and chemokines [4]. Eosinophils possess a variety of cell surface receptors for cell signaling associated with chemotaxis, adhesion, respiratory burst, degranulation, production of cytokines and chemokines, apoptosis or survival [5], all of which may be closely associated with eosinphil-mediated tissue inflammatory responses in helminth infection. Recent experimental studies have demonstrated that eosinophils can function as antigen-presenting cells (APCs). Eosinphils can process and present a variety of microbial, viral, and parasitic antigens [6].
Although the protective role of tissue eosinophilia against tissue-invasive helminths remains controversial, it is clear that eosinophils contribute to tissue inflammatory responses in helminthic infections. In this review, we summarize eosinophil responses to helminthic parasites and discuss the innate roles of eosinophils in related tissue inflammatory responses.

CARDINAL STRUCTURES OF EOSINOPHILS

Eosinophils are characterized by bilobed nuclei and four main granules [7]. The primary granule is the principal site of Charcot-Leyden Crystal protein (CLC; now identified as galectin-10) production [8]. It is possible that CLC is involved in the interactions between eosinphils and the abundant carbohydrate residues that parasitic worms carry on their surfaces [9]. Cytotoxic granular proteins include major basic protein (MBP), eosinphil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil neurotoxin (EDN), all of which reside within the crystalloid secondary granule along with a number of cytokines. Eosinophil lipid bodies (LB) contain 5-lipooxygenase, cyclooxygenase, leukotreine C4 (LTC4) synthase, and arachidonic acid (AA) for lipid mediator biosynthesis, as well as small granules that store proteins such as arylsulfase B and acid phosphatases.

EOSINOPHILIA IN HELMINTH INFECTION

Eosinophils originate from CD34+ cells in the bone marrow expressing the IL-5Rα-chain, regulated by the transcription factors GATA-1, GATA-2, and c/EBP [5]. With the help of IL-5, adhesion molecules, and eotaxin-1, eosinophils relocate into the peripheral circulation and travel to specific tissues, predominantly the gastrointestinal (GI) tract, thymus, and mammary glands, where eotaxin-1 is constitutively expressed [5]. The elevation of eosinophil levels in the peripheral circulation and tissues is observed in a wide variety of diseases including diseases of infectious, allergic, neoplastic, and idiopathic origins [10]. Parasitic helminth infections are the most common cause of persistent eosinophilia. Infections by helminths with life cycles that include tissue migratory phases, including trichinosis, ascariasis, filariasis, and paragonimiasis, induce sustained elevated eosinophilia in host blood and tissues. In contrast, sustained eosinophila is usually absent when hosts are infected by parasites that dwell outside the tissues, such as intralumen- (e.g., adult tapeworm), or intracyst- (e.g., Echinococcus spp.) dwelling species [10].

EOSINOPHIL TRAFFICKING AND HELMINTHIC PARASITES

It is evident that helminth-induced eosinophilia is accompanied by a profound change in the production of key regulatory cytokines (IL-5, IL-3, GM-CSF) and chemokine (eotaxin) [11]. Trichinella spiralis infection induces eosinophil recruitment to infected tissues that is dependent upon eotaxin-1 and -2 [12]. The eosinophils recruited into worm-infected tissues are further activated by various inflammatory stimuli, which may contribute to related eosinophil-mediated tissue inflammatory responses.
It was recently reported that serum levels of eotaxin are increased in human strongyloidiasis [13]. The numbers of positive cells expressing CCR3 receptors for eotaxin are increased during helminth infection [14]. Furthermore, helminths themselves secrete eosinophil-specific chemokinetic molecules showing galectin-like activity [15]. Mammalian galectin-9 is a potent eosinophil chemoattractant [16], and galectin-3 also plays a supporting role in eosinophil trafficking [17]. These results suggest that eosinophils respond to and are activated by worm-secreted factors mimicking mammalian galectin-9, which may amplify eosinophil trafficking to worm-infected tissues. This leads us to hypothesize that eosinophils are well-equipped innate immune cells capable of countering the attempts of parasitic worms to evade host immune responses.

DEGRANULATION AND HELMINTHIC PARASITES

The release of secondary granule proteins such as MBP, ECP, EPO, and EDN may directly damage tissues or infectious worms [5, 18]. Immunological stimuli, including sIgA, IgG, C5a, PAF, IL-5, IL-3, and GM-CSF can induce eosinophil degranulation [3]. However, the role of IgE in eosinophil degranulation remains controversial [19,20]. A recent report has shown that eosinophils from allergic donors express approximately 0.5% of the FcεRI that basophils express, and that eosinophils stimulated with human IgE or anti-human IgE do not exhibit effector functions such as production of leukotriene C4 or superoxide anion, or degranulation [20]. This suggests that helminth-induced IgE production is not critical for eosinphil degranulation, although degranulated eosinophils are frequently observed in the vicinity of damaged parasites in vivo.
There are three modes of eosinophil degranulation, including compound exocytosis, piecemeal degranulation, and cytolytic degranulation (necrosis) [7]. The release of granular proteins via compound exocytosis results from multiple fusions of granules in eosinophils with normal plasma membrane. PAF, which signals via the G-protein coupled receptor (GPCR), is the best-known stimulus for compound exocytosis. IL-5 can induce piecemeal degranulation, which is characterized by emptied secondary granules resulting from the slow leakage of granular proteins. Lastly, degranulation can occur by cytolytic mechanisms as a result of cell death. Recent reports have demonstrated that human eosinphils degranulate in response to helminth-derived excretory-secretory products (ESP) [21]. In particular, 27-kDa cysteine protease in the ESP secreted by newly excysted Paragonimus westermani metacercariae (PwNEM) induces EDN release from human eosinophils isolated from peripheral blood [22], whereas PwNEM-secreted 28-kDa cysteine protease did not induce eosinophil degranulation. In addition to their direct toxic effects on worms and tissues, granular proteins have been shown to regulate tissue inflammation by activating various immune cells. For example, MBP has been demonstrated to promote degranulation from mast cells via IgE-independent mechanisms, superoxide anion production, or release of IL-8 and lipid mediators including LTC4 and PGF2α from eosinophils, neutrophils, and epithelial cells [23]. These results suggest that release of granular proteins from eosinophils in response to specific proteases secreted by helminths play a role in eosinophil-mediated tissue inflammatory responses during tissue invasion by parasitic worms.

NADPH OXIDASE-DERIVED ROS AND HELMINTHIC PARASITES

In addition to toxic granule proteins such as ECP, MBP, and EDN, reactive oxygen species (ROS) are toxic compounds released by eosinophils. They are generated by the NOX family (NOX2) of NADPH oxidase [24], which can be stimulated by PMA, IL-3, IL-5, GM-CSF, C5a, PAF, and eotaxin [3]. It is interesting to note that the capacity of human eosinophils to produce and release ROS such as superoxide anions (O2-) is approximately tenfold higher than the capacity of neutrophils [25]. Recent reports have shown that human eosinophils can produce superoxide anions in response to helminth-derived cysteine proteases such as 27-kDa cysteine protease [22]. Besides the cytotoxic role of ROS, they also participate in inflammatory responses mediated by T cells and eosinophils [26,27]. These results suggest that ROS production by eosinophils stimulated by helminth-derived secretory products may contribute to eosinophil-mediated tissue inflammation in helminthic infection.

RELEASE OF LIPID MEDIATORS AND HELMINTHIC PARASITES

Human eosinophils isolated from peripheral blood produce both eicosanoids and PAF. The major eicosanoid produced by eosinophils is leukotriene C4 (LTC4), which is rapidly converted to LTD4 and LTE4 in the extracellular environment [28]. LTC4, LTD4, and LTE4 are collectively referred to as cysteinyl leukotrienes. These molecules contribute to the constriction of bronchi and increase airway responsiveness, vascular permeability, and mucus secretion in the airways of bronchial asthmatic patients.
In Nippostrongylus brasiliensis-infected mice, elevation in PAF synthesis is correlated with significant elevation in histologically detectable eosinophils in the jejunum [29]. Human eosinophils secrete LTC4 after adhering to IgG- or IgE-coated schistosomules of Schistosoma mansoni [30]. A recent report suggests that leukotrienes play a protective role in controlling parasite burden in murine strongyloidiasis [31]. However, there is no available information regarding whether eosinophils can be activated to release lipid mediators such as LTC4 or prostaglandin (PG) when directly stimulated by worm-derived secretions or products. Recently, there has been intriguing evidence that various parasites secrete lipid mediators to communicate with host immune cells [32]. In particular, eosinophils possess well-equipped cells bearing receptors for lipid mediators [33]. Therefore, further studies of the role of helminth-secreted lipid mediators on eosinophil-mediated tissue inflammation are warranted.

PRODUCTION OF CYTOKINES AND HELMINTHIC PARASITES

Human eosinophils produce cytokines, chemokines, and growth factors [5]. For example, cytokines include IL-1α, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-11, IL-12, IL-13, IL-16, IL-17, leukemia inhibitory factor, interferon-γ, tumor necrosis factor α (TNF-α, and GM-CSF. A variety of chemokines including epithelial cell-derived neutrophil activation peptide (ENA-78/CXCL5), eotaxin, growth-related oncogene (GROα/CXCL1), IL-8, IFN-γ-inducible protein (IP-10/CXCL10), IFN-inducible T-cell α chemoattractant (I-TAC/CXCL11), macrophage inflammation protein 1α(MIP-1α), monocyte chemoattractant protein 1 (MCP-1/CCL3), MCP-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5) are generated by eosinphils. Eosinophils produce growth factors such as heparin-binding epidermal growth factor-like binding protein (HB-EGF-LBP), nerve growth factor (NGF), plateletderived growth factor (PDGF), stem cell factor, transforming growth factor α (TGF-α) and TGF-β1. Among secreted proteins, IL-2, IL-4, IL-5, IL-6, TNF-α, GM-CSF, eotaxin, RANTES and TFG-α are stored as preformed mediators within eosinophil crystalloid granules [34]. It is interesting to note that eosinophils express two pro-inflammatory cytokines, IL-12 and IFN-γ, which serve to down-regulate allergic inflammation [5]. Indeed, IL-12 has been shown to inhibit allergen-induced Th2 cytokine responses [35] and eosinophil degranulation [36]. These results suggest that eosinophils may have the ability to release cytokines or chemokines for regulation of eosinophil-mediated tissue inflammation in helminth infection.
Recent studies have demonstrated that helminthic parasites can regulate immune responses via the production of cytokines. For example, infection with Fasciola hepatica has been demonstrated to attenuate autoimmunity via TGF-β-mediated immune suppression of Th17 and Th1 responses [37]. In addition, Th2 cell-derived IL-4 production facilitates eosinophil and lymphocyte recruitment and Th2 cytokine production associated with N. brasiliensis infections [38]. Infection with Strongyloides stercoralis induces enhanced serum levels of eotaxin and IL-5 [13]. However, information regarding cytokine production by eosinophils in response to helminthic parasites is limited. Recently, we have shown that P. westermani-secreted products directly stimulate human eosinophils to produce GM-CSF [39] and IL-8 [40]. GM-CSF plays an important role in maintaining the viability and inducing the effector function of eosinophils [3,41]. In addition, IL-8 is a highly potent chemotactic cytokine for eosinophils as well as neutrophils [42]. It is of particular that that lower, but not higher concentrations of ESP secreted by PwNEM exhibit strong stimulatory effects on the production of GM-CSF and IL-8 by human eosinophils [39,40]. The stimulatory effect of the ESP on autocrine production of GM-CSF is nicely matched with enhanced longevity of eosinophils [39]. These results suggest that eosinophils may be actively responded to the light infection of the worms to release cytokines or chemokines associated with induction of eosinophil-mediated tissue inflammation, which might pain the worms to lose their original way to final destination. In contrast, eosinophils seem to be passively responded in response to the heavy infection to silence eosinophil's responses which might be favorable for host to block the severe tissue damage. In our previous study [39], we also found an interesting result that pretreatment of high concentrations of the ESP secreted by PwNEM with heat at 100℃ for 5 min showed a pro-survival effect on eosinophils [39]. This suggests that eosinophils may be directly activated by heat-resistant molecules secreted by helminthic parasites to release cytokines and chemokines, which in turn may play a role in promoting eosinophil-mediated tissue inflammatory responses during helminth infection. Further studies on this issue are required.

APOPTOSIS AND HELMINTHIC PARASITES

The life span of eosinophils may be prolonged in the presence of IL-5 GM-CSF, IL-3 [41], IL-9 [43], IL-13 [44], IL-33 [45], lipid mediators such as PGE2 [46], and microbial-derived lipopolysaccharides (LPS) [47]. In contrast, eosinophils undergo spontaneous death through apoptosis within four days without the presence of eosinophil active cytokines in vitro. In order to assess the innate role of eosinophils in helminth infection, recent studies have focused on the direct effects of helminthsecreted products on the viability of human eosinophils. It has been demonstrated that P. westermani- or F. hepatica-secreted ESP induces apoptosis of eosinophils in a caspase-dependent manner [48,49]. Moreover, F. hepatica-derived ESP has been reported to cause mitochondrial-membrane depolarization of eosinophils leading to the release of cytochrome c, and also induced intracellular ROS generation, which preceded mitochondrial injury for apoptosis [50]. Since most apoptotic tissue eosinophils progress to the pro-inflammatory cellular fate of secondary necrosis [51], it is possible that eosinophil apoptosis induced by helminth-derived ESP may cause severe tissue inflammation that helps to combat infectious worms. P. westermani-secreted ESP has also death effect on eosinophils stimulated with pro-survival cytokines including GM-CSF, IL-5 and IL-3 [48]. The pro-death effect the ESP was completely abolished by heat treatment. These results suggest that heat labile factors contained in the helminth-derived ESP can induce eosinophil apoptosis, which may be closely associated with orchestration of eosinophil-mediated tissue inflammation for host defense against tissue migratory helminthic worms. Further studies are necessary to determine what factors secreted by helminthic worms and how trigger the pro-apoptotic signals associated with eosinophil death.

MECHANISMS THAT HELMINTHIC PARASITES USE TO EVADE EOSINPHIL-MEDIATED HELMINTHOTOXICITY

Helminth-derived products harbor specific components leading to the down-regulation of eosinophil- or mast cell-associated allergic responses. This allows parasitic worms to evade host immune responses. For example, the immunization of proteins from adult Toxascaris leonine inhibits allergic specific Th2 response [52]. Anisakis simplex-derived peptide has also been found to inhibit eosinophil-mediated inflammatory responses in the airways in ovalbumin-induced bronchial asthmatic mice [53]. Heligmosomoides polygyrus infection down-regulates eotaxin concentrations and CCR3 expression in lung eosinophils in a allergic pulmonary inflammation mouse model [54].
Recent reports have suggested that helminthic worms themselves secrete specific molecules to interfere with eosinophilmediated tissue inflammatory responses during helminth infection. For example, Toxocara canis larval excretory/secretory proteins impair the eosinophil-dependent resistance of mice to N. brasiliensis [55]. P. westermani-derived proteases attenuate the effector functions of eosinphils triggered by IgG [56]. Cathepsin L proteinase secreted by F. hepatica prevents antibody-mediated eosinophil attachment to newly excysted juveniles in vitro [57]. Moreover, eosinophil selective chemokine eotaxin has been re-ported to be specifically cleaved by hookworm metalloproteases, which block the chemotactic effects on eosinophils in vitro and in vivo [58]. Furthermore, it is interesting to note that filarial nematode-secreted products inhibit IgE-mediated mast cell responses [59], considering the fact that there are immunological interactions between human eosinophils and mast cells [60]. These results suggest that tissue-migratory helminthic parasite-secreted products might contribute to reduction of eosinophil-mediated tissue inflammation, which provides an immunological milieu for the worms to complete their long journey during the tissue-migratory phase in vivo.

CONCLUSION

Eosinophils are end-stage cells that reside in mucosal tissues and function in host defense against helminth infection. Recent studies regarding immunological interactions between eosinophils and helminthic parasites have made important advances in understanding the innate role of eosinophils in controlling eosinophil-associated tissue inflammation involved in infection by tissue migratory helminthic parasites. In this review, we emphasize two points. The first is that eosinophils are well-equipped immune cells that directly recognize helminth-derived immunomodulating agents and mount tissue inflammatory responses for host defense. The second is that tissue-migratory helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival in hosts. Future studies regarding the signaling mechanisms of cross talk between hosts and parasitic worms are warranted. Furthermore, deeper investigation to elucidate the role of galectin-10, which is expressed on the surface of eosinophils, in host defense against helminthic parasites is recommended.

REFERENCES

1. Wynn TA, Thompson RW, Cheever AW, Mentink-Kane MM. Immunopathogenesis of schistomiasis. Immunol Rev 2004;201: 156-167. PMID: 15361239.
crossref pmid
2. Rosenberg HF, Phipps S, Foster PS. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol 2007;119: 1303-1310. PMID: 17481712.
crossref pmid
3. Horie S, Gleich GJ, Kita H. Cytokines directly induce degranulation and superoxide production from human eosinophils. J Allergy Clin Immunol 1996;98: 371-381. PMID: 8757214.
crossref pmid
4. Kita H. The eosinophils: a cytokine-producing cells? J Allergy Clin Immunol 1996;97: 889-892. PMID: 8655882.
crossref pmid
5. Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P, Kay AB, Rothenberg ME. Eosinophils: Biological properties and role in health and disease. Clin Exp Allergy 2008;38: 709-750. PMID: 18384431.
crossref pmid
6. Shi HZ. Eosinophils function as antigen-presenting cells. J Leukoc Biol 2004;76: 520-527. PMID: 15218055.
crossref pmid
7. Dvorak AM, Weller PF. Ultrastructural analysis of human eosinphils. Chem Immunol 2000;76: 1-28. PMID: 10761302.
crossref pmid
8. Ackerman SJ, Liu L, Kwatia MA, Savage MP, Leonidas DD, Swaminthan GJ, Acharya KR. Charcot-Leuden crystal protein (galectin-10) is not a dual function galectin with lysophopholipase activity but binds a lysophosphoslipase inhibitor in a novel structural fashin. J Biol Chem 2002;277: 14859-14868. PMID: 11834744.
crossref
9. Young AR, Barcham GJ, Kemp JM, Dunphu JL, Nash A, Meeusen EN. Functional characterization of an eosinophil-specific galectin, ovine galectin-14. Glycoconj J 2009;26: 423-432. PMID: 18810635.
crossref pmid
10. Nutman TB. Evaluation and differential diagnosis of marked, persistent eosinophilia. Immunol Allergy Clin North Am 2007;27: 529-549. PMID: 17868863.
crossref pmid pmc
11. Fulkerson PC, Rothenberg ME. Origin, regulation and physiological function of intestinal eosinophils. Best Pract Res Clin Gastroenterol 2008;22: 411-423. PMID: 18492563.
crossref pmid pmc
12. Bruschi F, Korenaga M, Watanabe N. Eosinophils and Trichinella infection: toxic for the parasite and the host. Trend Parasitol 2008;24: 462-467.
crossref pmid
13. Mir A, Benahmed D, Igual R, Borras R, O'Connor JE, Moreno MJ, Rull S. Eosinophil-selective mediators in human strongyloidiasis. Parasite Immunol 2006;28: 397-400. PMID: 16879311.
crossref pmid
14. Litvinova LS, Riazantseva NV, Novitskii VV. Dysregulation of cooperative interactions of immunocytes and eosinophils in the mechanism of development of eosinophilia in Opisthorchis felineus invasion. Med Parazitol (Mosk) 2008;3: 13-17. PMID: 18819423.

15. Tuner DG, Wildblood LA, Inglis NF, Jones DG. Characterization of a galectin-like activity from the parasitic nematode, Haemonchus contortus, which modulates ovine eosinphil migration in vitro. Vet Immunol Immunopathol 2008;122: 138-145. PMID: 18187208.
crossref pmid
16. Matsushita N, Nishi N, Seki M, Matsumoto R, Kuwavara I, Liu FT, Hata Y, Nakamura T, Hirashima M. Requirement of divalent galactoside-binding activity of ecalectin/galectin-9 for eosinophil chemoattraction. J Biol Chem 2000;275: 8355-8360. PMID: 10722666.
crossref
17. Rao SP, Wang Z, Zuberi RI, Sikora L, Bahaie NS, Zuraw BL, Liu FT, Sriramarao P. Galectin-3 functions as an adhesion molecules to support eosinophil rolling and adhesion under conditions of flow. J Immunol 2007;179: 7800-7807. PMID: 18025226.
crossref pmid
18. Ramos AL, Discipio RG, Ferreira AM. Eosinophil cationic protein damages protoscoleces in vitro and is present in the hydatid cyst. Parasite Immunol 2006;28: 347-355. PMID: 16879306.
crossref pmid
19. Gounni AS, Lamkhioued B, Ochiai K, Tanaka Y, Delaporte E, Capron A, Kinet JP, Capron M. High-affinity IgE receptor on eosinophils is involved in defense against parasites. Nature 1994;367: 183-186. PMID: 8114916.
crossref
20. Kita H, Kaneko M, Bartemes KR, Weiler DA, Schimming AW, Reed CE, Gleich GJ. Does IgE bind to and activate eosinophils from patients with allergy? J Immunol 1999;162: 6901-6911. PMID: 10352312.
pmid
21. Shin MH, Chung YB, Kita H. Degranulation of human eosinophils induced by Paragonimus westermani-secreted protease. Korean J Parasitol 2005;43: 33-37. PMID: 15793357.
crossref pmid pmc
22. Chung YB, Kita H, Shin MH. A 27 kDa cysteine protease secreted by newly excysted Paragonimus westermani metacercariae induces superoxide anion production and degranulation of human eosinophils. Korean J Parasitol 2008;46: 95-99. PMID: 18552546.
crossref pmid pmc
23. Thomas LL, Page SM. Inflammatory cell activation by eosinophil granule proteins. Chem Immunol 2000;76: 99-117. PMID: 10761307.
crossref pmid
24. Krause KH. Tissue distribution and putative physiological function of NOX family NADPH oxidases. Jpn J Infect Dis 2004;57: S28-S29. PMID: 15507765.
pmid
25. Someya A, Nishijima K, Nunoi H, Irie S, Nagoaka I. Study on the superoxide-producing enzymes of eosinphils and neutrophils: Comparison of the NADPH oxidase components. Arch Biochem Biophys 1997;345: 207-213. PMID: 9308891.
crossref
26. Los M, Droge W, Stricker K, Baeuerle PA, Schulze Osthoff K. Hydrogen peroxide as a potent activator of T lymphocyte functions. Eur J Immunol 1995;25: 159-165. PMID: 7843227.
crossref pmid
27. Lee YA, Shin MH. Mitochondrial respiration is required for activation of ERK1/2 and caspase-3 in human eosinophils stimulated with hydrogen peroxide. J Invest Allergol Clin Immunol 2009;19: 188-194.
pmid
28. Triggiani M, Calabrese C, Granata F, Gentile M, Marone G. Metabolism of lipid mediators in human eosinophils. Chem Immunol 2000;76: 77-98. PMID: 10761306.
crossref pmid
29. Hoquboan CM, Befus AD, Wallace JL. Intestinal platelet-activation factor synthesis during Nippostrongylys brasiliensis infection in the rat. 1991;4: 211-224.

30. Moqbel R, Macdonald AJ, Cromwell O, Kay AB. Release of leukotriene C4 (LTC4) from human eosinophils following adherence to IgE- and IgG-coated schistosomula of Schistosoma mansoni. Immunology 1990;69: 435-442. PMID: 2312166.
pmid pmc
31. Machado ER, Veta MT, Lourenco EV, Anibal FF, Sorgi CA, Soares EG, Roque-Barreira MC, Medeiros AI, Faccioli LH. Leukotrines play a role in the control of parasite burden in murine strongyloidiasis. J Immunol 2005;175: 3892-3899. PMID: 16148135.
crossref pmid
32. Kubata BK, Duszenko M, Martin KS, Urade Y. Molecular basis for prostaglandin production in hosts and parasites. Trend Parasitol 2007;23: 325-331.
crossref pmid
33. Mita H, Hasegawa M, Higashi N, Akiyama K. Characterization of PGE2 receptor subtypes in human eosinophils. J Allergy Clin Immunol 2002;110: 457-459. PMID: 12209094.
crossref pmid
34. Lacy P, Moqbel R. Eosinophil cytokines. Chem Immunol 2000;76: 134-155. PMID: 10761309.
crossref pmid
35. Gavett SH, O'Hearn DJ, Li X, Huang SK, Finkelman FD, WillsKarp M. Interleukin-12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice. J Exp Med 1995;182: 1527-1536. PMID: 7595222.
crossref pmid pmc
36. Davoine F, Ferland C, Chakir J, Lee JE, Adamko DJ, Moqbel R, Laviolette M. Interleukin-12 inhibits eosinophil degranulation and migration but does not promote eosinophil apoptosis. Int Arch Allergy Immunol 2006;140: 277-284. PMID: 16735797.
crossref pmid
37. Walsh KP, Brady MT, Finlay CM, Boon L, Mils KH. Infection with a helminth parasite attenuates autoimmunity through TGF-β-mediated immune suppression of Th17 and Th1 responses. J Immunol 2009;183: 1577-1586. PMID: 19587018.
crossref pmid
38. Mearns S, Horsnell WG, Hoving JC, Dewals B, Cutler AJ, Kirstein F, Myburgh E, Arendse B, Brombacher F. Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology. Infect Immun 2008;76: 5535-5542. PMID: 18809669.

39. Shin MH, Seoh JY, Park HY, Kita H. Excretory-secretory products secreted by Paragonimus westermani delay the spontaneous cell death of human eosinophils through autocrine production of GM-CSF. Int Arch Allergy Immunol 2003;132: 48-57. PMID: 14555858.
crossref pmid
40. Shin MH, Lee SY. Proteolytic activity of cysteine protease in excretory-secretory product of Paragonimus westermani newly excysted metacercariae pivotally regulates IL-8 production of human eosinophils. Parasite Immunol 2000;22: 529-533. PMID: 11012979.
crossref pmid
41. Tai PC, Sun L, Spry CJ. Effects of IL-5, granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-3 on the survival of human blood eosinophils in vitro. Clin Exp Immunol 1991;85: 312-326. PMID: 1864012.
crossref pmid pmc
42. Lampinen M, Rak S, Venge P. The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung. Clin Exp Allergy 1999;29: 314-322. PMID: 10202337.
crossref pmid
43. Gounni AA, Gregory B, Nutku E, Aris F, Latifa K, Minshall E, North J, Tavernier J, Levit R, Nicolaides N, Robinson D, Hamid Q. Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils. Blood 2000;96: 2163-2171. PMID: 10979962.
pmid
44. Horie S, Okubo Y, Hossain M, Sato E, Nomura H, Koyama S, Suzuki J, Isobe M, Sekiguchi M. Interleukin-13 but not interleukin-4 prolongs eosinphil survival and induces eosinophil chemotaxis. Intern Med 1997;36: 179-185. PMID: 9144009.
crossref pmid
45. Suzukawa M, Koketsu R, Iikura M, Nakae S, Matsumoto K, Nagase H, Saito H, Matsushima K, Ohta K, Yamamoto K, Yamaguchi M. Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinphils. Lab Invest 2008;88: 1245-1253. PMID: 18762778.
crossref pmid
46. Peacock CD, Misso NL, Watkins DN, Thompson PJ. PGE2 and dibutyryl cyclic adenosine monophosphate prolong eosinophil survival in vitro. J Allergy Clin Immunol 1999;104: 153-162. PMID: 10400853.
crossref pmid
47. Meerschaert J, Busse WW, Bertics PJ, Mosher DF. CD14+ cells are necessary for increased survival of eosinophils in response to lipopolysaccharide. Am J Respir Cell Mol Biol 2000;23: 780-787. PMID: 11104731.
crossref pmid
48. Min DY, Lee YA, Ryu JS, Ahn MH, Chung YB, Sim S, Shin MH. Caspase-3-mediated apoptosis of human eosinophils by the tissue-invading helminth Paragonimus westermani. Int Arch Allergy Immunol 2004;133: 357-364. PMID: 15031609.
crossref pmid
49. Serradell MC, Guasconi L, Cervi L, Chiapello LS, Masih DT. Excretory-secretory products from Fasciola hepatica induce eosinophil apoptosis by a caspase-dependent mechanism. Vet Immunol Immunopathol 2007;117: 197-208. PMID: 17449115.
crossref pmid
50. Serradell MC, Guasconi L, Masih DT. Involvement of mitochondrial pathway and key role of hydrogen peroxide during eosinophil apoptotosis induced by excretory-secretory products from Fasciola hepatica. Mol Biochem Parasitol 2009;163: 96-106.
crossref pmid
51. Uller L, Rydell-Tormanen K, Persson CG, Erjefalt JS. Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils aggravate rather than resolve established inflammation. Respir Res 2005;6: 90-103. PMID: 16086832.
crossref pmid pmc
52. Lee KH, Park HK, Jeong HJ, Park SK, Lee SJ, Choi SH, Cho MK, Ock MS, Hong YC, Yu HS. Immunization of proteins from Toxascaris leonine adult worms inhibits allergic Th2 responses. Vet Parasitol 2008;156: 216-225. PMID: 18653284.
crossref pmid
53. Park SK, Cho MK, Park HK, Lee KH, Lee SJ, Choi SH, Ock MS, Jeong HJ, Lee MH, Yu HS. Macrophage migration inhibitory factor homologes of Anisakis simplex suppress Th2 responses in allergic airway inflammation model via CD4+CD25+Foxp3+ T cell recruitment. J Immunol 2009;182: 6907-6914. PMID: 19454687.
crossref pmid
54. Rzepecka J, Donskow-Schmelter K, Doligalska M. Heligmosmoides polygyrus infection down-regulates eotaxin concentration and CCR3 expression on lung eosinophils in murine allergic pulmonary inflammation. Parasite Immunol 2007;29: 405-413. PMID: 17650182.
crossref pmid
55. Giacomin PR, Cava M, Tumes DJ, Gauld AD, Iddawela DR, McColl SR, Parsons JC, Gordon DL, Dent LA. Toxocara canis larval excretory-secretory proteins impair eosinophil-dependent resistance of mice to Nippostrongylus brasiliensis. Parasite Immunol 2008;5. 26. [Epub ahead of print].

56. Shin MH, Kita H, Park HY, Seoh JY. Cysteine protease secreted by Paragonimus westermani attenuates effector functions of human eosinophils stimulated with immunoglobulin G. Infect Immun 2001;69: 1599-1604. PMID: 11179333.
crossref pmid pmc
57. Carmona C, Dowd AJ, Smith AM, Dalton JP. Cathepsin L proteinase secreted by Fasciloa hepatica in vitro prevents antibody-mediated eosnophil attachemment to newly excysted juveniles. Mol Biochem Parasitol 1993;62: 9-17. PMID: 8114830.
crossref pmid
58. Culley FJ, Brown A, Conroy DM, Sabroe I, Pritchard DI, Williams TJ. Eotaxin is specifically cleaved by hookworm metalloproteases preventing its action in vitro and in vivo. J Immunol 2000;165: 6447-6453. PMID: 11086084.
crossref pmid
59. Melendez AJ, Harnett MM, Pushparaj PN, Wong WS, Tay HK, McSharry CP, Harnett W. Inhibition of Fc epsilon RI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes. Nat Med 2007;13: 1375-1381. PMID: 17952092.
crossref pmid
60. Levi-Schaffer F. Cross talk between mast cells and eosinophils. Allergy 1999;54(Suppl 58):36-38. PMID: 10735648.
crossref
Editorial Office
Department of Molecular Parasitology, Samsung Medical Center, School of Medicine, Sungkyunkwan University,
2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea.
Tel: +82-31-299-6251   FAX: +82-1-299-6269   E-mail: kjp.editor@gmail.com
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
Copyright © 2022 by The Korean Society for Parasitology and Tropical Medicine.     Developed in M2PI