The debate over the effector function of eosinophils in helminth infection: new evidence from studies on the regulation of vaccine immunity by IL-12

Wynn, Thomas A.

doi:10.1590/s0074-02761997000800014

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…Parasitic helminth infections are characterized by mast cell hyperplasia, eosinophilia (12), and markedly elevated levels of circulating antigen-nonspecific IgE (13), which are a form of helminth protection (14,15). Parasitic antigen-specific IgE is associated with elimination of parasites from infected hosts, while antigennonspecific polyclonal IgE may be involved in the survival of invading parasites (14,16).…”

Section: Discussionmentioning

confidence: 99%

A Factor of Inducing IgE from a Filarial Parasite Prevents Insulin-Dependent Diabetes Mellitus in Nonobese Diabetic Mice

Imai

Tezuka

Fujita

2001

Biochemical and Biophysical Research Communications

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Section: Discussionmentioning

confidence: 99%

A Factor of Inducing IgE from a Filarial Parasite Prevents Insulin-Dependent Diabetes Mellitus in Nonobese Diabetic Mice

Imai

Tezuka

Fujita

2001

Biochemical and Biophysical Research Communications

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“…Exogenous administration of IL-12 during immunization with S. mansoni-egg antigen, irradiated cercariae or soluble worm antigen preparation (SWAP) also can reduce subsequent egg-induced lung pathology [10] and modulation of Th1/Th2 responses [11], suggesting that this cytokine may be useful for promoting both humoral and cell-mediated protective responses against schistosomiasis [12,13]. In addition to the use of IL-12 protein, IL-12 plasmid DNA has been used as an adjuvant [14], where it elicited significant levels of protective immunity against S. japonica challenge infection [15].…”

Section: Introductionmentioning

confidence: 99%

Using poly-N-acetyl glucosamine gel matrix to deliver IL-12 with anti-schistosomasis vaccination

Salem

Attia

Al-Bolkiny

et al. 2010

J Infect Dev Ctries

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Background: Interleukin (IL)-12 is a potential adjuvant in a variety of diseases including schistosomiasis. The clinical use of IL-12, however, is limited by the toxicity associated with its systemic administration. We have developed a novel delivery system (designated F2 gel matrix) composed of poly-N-acetyl glucosamine that has the dual properties of sustaining the release of proteins (e.g. interleukins) and adjuvant effects. The main aim of this study was to use a mouse model to test whether IL-12 released from F2 gel can induce adjuvant effects in the schistosomiasis setting as compared to those obtained after systemic delivery of IL-12. Methodology: First, we compared the toxicity induced by paracrine (delivered by F2 gel) and systemic IL-12. Second, we compared the induction of cytokines induced by paracrine and systemic IL-12. Third, we compared the adjuvant effects of paracrine and systemic IL-12-based prophylactic vaccination against schistosomiasis using soluble worm antigen preparation (SWAP). Results: IL-12 released from F2 gel did not induce significant toxicity measured by alanine aminotransferase (ALT). We found similar serum levels of IFN-γ, TNF-α and IL-2 after paracrine and systemic IL-12 treatments. We also found that vaccination with F2 gel/SWAP/IL-12 induced higher anti-schistosomal effects than IL-12/SWAP as evidenced by 1) the decrease in the total liver egg counts; 2) the reduction in the granuloma size and fibrotic reaction in the liver; and 3) the amelioration of the liver functions. Conclusion: Collectively, these results indicate that IL-12-F2 gel delivery approach could be considered as a potential strategy for the treatment of schistosomiasis.

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“…It is has been debated whether they are involved directly in the killing of worms or in orchestrating the immune response (13,19,31,45).…”

mentioning

confidence: 99%

Lack of Eosinophil Peroxidase or Major Basic Protein Impairs Defense against Murine Filarial Infection

Specht¹,

Saeftel²,

Arndt

et al. 2006

Infect Immun

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Eosinophils are a hallmark of allergic diseases and helminth infection, yet direct evidence for killing of helminth parasites by their toxic granule products exists only in vitro. We investigated the in vivo roles of the eosinophil granule proteins eosinophil peroxidase (EPO) and major basic protein 1 (MBP) during infection with the rodent filaria Litomosoides sigmodontis. Mice deficient for either EPO or MBP on the 129/SvJ background developed significantly higher worm burdens than wild-type mice. Furthermore, the data indicate that EPO or MBP is involved in modulating the immune response leading to altered cytokine production during infection. Thus, in the absence of MBP, mice showed increased interleukin-10 (IL-10) production after stimulation of macrophages from the thoracic cavity where the worms reside. In addition to elevated IL-10 levels, EPO ؊/؊ mice displayed strongly increased amounts of the Th2 cytokine IL-5 by CD4 T cells as well as a significantly higher eosinophilia. Interestingly, a reduced ability to produce IL-4 in the knockout strains could even be seen in noninfected mice, arguing for different innate propensities to react with a Th2 response in the absence of either EPO or MBP. In conclusion, both of the eosinophil granule products MBP and EPO are part of the defense mechanism against filarial parasites. These data suggest a hitherto unknown interaction between eosinophil granule proteins, defense against filarial nematodes, and cytokine responses of macrophages and CD4 T cells.

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The debate over the effector function of eosinophils in helminth infection: new evidence from studies on the regulation of vaccine immunity by IL-12

Abstract: The production of

Cited by 9 publications

References 24 publications

A Factor of Inducing IgE from a Filarial Parasite Prevents Insulin-Dependent Diabetes Mellitus in Nonobese Diabetic Mice

A Factor of Inducing IgE from a Filarial Parasite Prevents Insulin-Dependent Diabetes Mellitus in Nonobese Diabetic Mice

Using poly-N-acetyl glucosamine gel matrix to deliver IL-12 with anti-schistosomasis vaccination

Lack of Eosinophil Peroxidase or Major Basic Protein Impairs Defense against Murine Filarial Infection

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