Immunology of Human Helminth Infection

Allen, Judith E.; Maizels, Rick M.

doi:10.1159/000237225

Cited by 138 publications

(94 citation statements)

References 48 publications

(61 reference statements)

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“…Eosinophilia has been pointed out as a hallmark of many helminthic infections, including S. mansoni (David et al 1980, Allen & Maizels 1996, Heukelbach et al 2006. During acute S. mansoni infection, both in experimental models and humans the cellular infiltrate typically observed on hepatic granuloma is constituted predominantly by eosinophils and monocytes (Bogliolo 1959, MacLaren et al 1987.…”

Section: Discussionmentioning

confidence: 99%

High expression of co-stimulatory and adhesion molecules are observed on eosinophils during human Schistosoma mansoni infection

Silveira-Lemos

Teixeira-Carvalho

Martins‐Filho

et al. 2006

Mem. Inst. Oswaldo Cruz

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Herein we have focused attention on major phenotypic features of peripheral blood eosinophils from chronic Schistosoma mansoni-infected patients. For this purpose, detailed immunophenotypic profiles of a range of cell surface markers were performed, including activation markers (CD23/CD69/CD25/HLA-DR), co-stimulatory molecules (CD28/CD80/CD86), chemokine receptors (CXCR1/CXCR2/CCR3/CCR5) besides L-selectin-CD62L and adhesion molecules (CD18/CD54). Our major findings pointed out increased frequency of CD23 + -cells, besides decreased percentages of CD69 + -eosinophils, suggesting a chronic activation status with low frequency of early activated eosinophils in chronic S. mansoni-infected patients (INT) in comparison to non-infected individuals (NI). Moreover, a dichotomic expression of beta-chemokine receptors was observed during human schistosomiasis mansoni with higher CCR5 and lower levels of CCR3 observed between groups. Enhanced expression of co-stimulatory receptors (CD28/CD86) and adhesion molecules (CD54/CD18), besides striking lower frequency of L-selectin + were reported for eosinophils from INT group as compared to NI. Interestingly, the frequency of CD62L + -eosinophils and a range of cell activation related molecules pointed out an opposite pattern of association in NI and INT, where only INT patients that display lower frequency of CD62L + -eosinophils (first CD62L tertile) kept the unusual relationship between the expression of L-selectin and the CD23 activation marker. These findings suggest that distinct dynamic of activation markers expressed by eosinophils may occur during chronic S. mansoni infection.Key words: schistosomiasis -eosinophils -activation markers -L-selectin Eosinophils have been shown to play a major role in the immune response to helminthic infections (Butterworth et al. 1979, Hamann et al. 1987. In this context, transendothelial migration is essential for eosinophil recruitment from blood vessels into inflammatory tissues. At the inflammatory site, further interaction with invading parasites occurs via adherence with subsequent larval damage mediated by release of eosinophil toxic granular effector molecules, proinflammatory lipids, and cytokines (Greene et al. 1981, Medina-De la Garza et al. 1990, Strote et al. 1990, Brattig et al. 1991, Wildenburg et al. 1994. The prerequisite for adherence of effector eosinophils to parasite's larval stages is their sequential activation and chemotactic attraction that favor the eosinophils tethering. The migration of mature activated eosinophils from circulatory pools into the inflammatory foci depends on specific upregulation of adhesion molecules and chemokine receptors, which direct transmigration through a positive chemotactic gradient. This phenomenon seems to represent the key element for eosinophils recruitment that lead to accumulation of these proinflammatory cells that surround the parasite in its microenvironment (Pearlman 1997, Tachimoto et al. 2000.The profile of cell surface molecules expression on mature eosinophils resembles...

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Section: Discussionmentioning

confidence: 99%

High expression of co-stimulatory and adhesion molecules are observed on eosinophils during human Schistosoma mansoni infection

Silveira-Lemos

Teixeira-Carvalho

Martins‐Filho

et al. 2006

Mem. Inst. Oswaldo Cruz

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“…IL-5 has been shown to have an additional role for activation and Ab secretion from mouse, but not human, CD5 ϩ B-1 cells, which produce IgM Abs (5,6). Prominent sources of IL-5 include T cells, mast cells, eosinophils, and NK cells (1,3), and several immune responses have been associated with an elevation of IL-5, such as allergy and asthma (7), malignant hyperplasia (8), autoimmune disease (4), and parasitic infection (9). The role of IL-5 has been highly debated due to its involvement in various responses considered to be either pathogenic or protective for the host.…”

mentioning

confidence: 99%

“…The role of IL-5 has been highly debated due to its involvement in various responses considered to be either pathogenic or protective for the host. Parasitic helminth infections have often been correlated with an increase in serum IL-5 levels, peripheral blood eosinophils, and eosinophil infiltration of host tissue where the parasites are located (4,9), but their role in parasite killing is still unclear.…”

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confidence: 99%

Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

Herbert

Lee

et al. 2000

The Journal of Immunology

112

110

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Protective immunity to Strongyloides stercoralis infective larvae in mice has been shown to be dependent on IL-5 based on mAb depletion studies. The goal of this study was to determine the functional role of IL-5 during the innate and adaptive immune response to larval S. stercoralis in mice. In these studies, three strains of mice were used: wild-type C57BL/6J (WT), IL-5 knockout (KO), and IL-5 transgenic (TG). Innate responses to the larvae indicated that there was enhanced survival in the KO animals and decreased survival in the TG animals compared with WT. Furthermore, killing of larvae in TG mice was associated with eosinophil infiltration and degranulation. In studying the adaptive immune response, it was observed that immunization of KO mice did not lead to the development of protective immunity. Experiments were then performed to determine whether KO mice reconstituted with Abs or cells could then develop protective immunity. KO mice displayed protective immunity via a granulocyte-dependent mechanism following injection of purified IgM from immune wild-type animals. Immunity in KO mice could also be reconstituted by the injection of eosinophils at the time of immunization. These eosinophils did not participate in actively killing the challenge infection, but rather were responsible for the induction of a protective Ab response. We conclude that IL-5 is required in the protective immune response for the production of eosinophils, and that eosinophils were involved in larval killing during innate immunity and in the induction of protective Abs in the adaptive immune response.

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“…Parasitic helminths characteristically induce chronic infections that may last for many years, despite the activation of the host immune response apparent in elevated serum IgE concentrations and eosinophilia (19). In vitro, the combination of eosinophils and immune serum is sufficient to activate eosinophils to kill helminth parasites by release of their toxic granule contents.…”

mentioning

confidence: 99%

Eotaxin Is Specifically Cleaved by Hookworm Metalloproteases Preventing Its Action In Vitro and In Vivo

Culley

Brown

Conroy

et al. 2000

The Journal of Immunology

132

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Eotaxin is a potent eosinophil chemoattractant that acts selectively through CCR3, which is expressed on eosinophils, basophils, mast cells, and Th2-type T cells. This arm of the immune system is believed to have evolved to control helminthic parasites. We hypothesized that helminths may employ mechanisms to inhibit eosinophil recruitment, to prolong worm survival in the host. We observed that the excretory/secretory products of the hookworm Necator americanus inhibited eosinophil recruitment in vivo in response to eotaxin, but not leukotriene B4, a phenomenon that could be prevented by the addition of protease inhibitors. Using Western blotting, N. americanus supernatant was shown to cause rapid proteolysis of eotaxin, but not IL-8 or eotaxin-2. N. americanus homogenate was fractionated by gel filtration chromatography, and a FACS-based bioassay measured the ability of each fraction to inhibit the activity of a variety of chemokines. This resulted in two peaks of eotaxin-degrading activity, corresponding to ∼15 and 50 kDa molecular mass. This activity was specific for eotaxin, as responses to other agonists tested were unaffected. Proteolysis of eotaxin was prevented by EDTA and phenanthroline, indicating that metalloprotease activity was involved. Production of enzymes inactivating eotaxin may be a strategy employed by helminths to prevent recruitment and activation of eosinophils at the site of infection. As such this represents a novel mechanism of regulation of chemokine function in vivo. The existence of CCR3 ligands other than eotaxin (e.g., eotaxin-2) may reflect the evolution of host counter measures to parasite defense systems.

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Immunology of Human Helminth Infection

Cited by 138 publications

References 48 publications

High expression of co-stimulatory and adhesion molecules are observed on eosinophils during human Schistosoma mansoni infection

High expression of co-stimulatory and adhesion molecules are observed on eosinophils during human Schistosoma mansoni infection

Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

Eotaxin Is Specifically Cleaved by Hookworm Metalloproteases Preventing Its Action In Vitro and In Vivo

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