Natural death of adult Onchocerca volvulus and filaricidal effects of doxycycline induce local FOXP3+/CD4+ regulatory T cells and granzyme expression

Korten, Simone; Badusche, Marlis; Büttner, Dietrich W.; Hoerauf, Achim; Brattig, Norbert W.; Fleischer, Bernhard

doi:10.1016/j.micinf.2007.12.004

Cited by 36 publications

(37 citation statements)

References 33 publications

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“…Importantly, localized Treg induction around parasite nodules in tissues has been seen (148), and T cell clones from these granulomas or PBMCs included many that expressed IL-10 and/or TGF-␤ (68,245). The role of DCs in inducing regulatory T cell responses is illustrated by the action of schistosome lysophosphatidylserine, which acts on human DCs to promote IL-10-producing Tr1 cells (290).…”

Section: Regulatory Cell Populations In Human Infectionmentioning

confidence: 99%

Helminth Infections and Host Immune Regulation

2012

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SUMMARY Helminth parasites infect almost one-third of the world's population, primarily in tropical regions. However, regions where helminth parasites are endemic record much lower prevalences of allergies and autoimmune diseases, suggesting that parasites may protect against immunopathological syndromes. Most helminth diseases are spectral in nature, with a large proportion of relatively asymptomatic cases and a subset of patients who develop severe pathologies. The maintenance of the asymptomatic state is now recognized as reflecting an immunoregulatory environment, which may be promoted by parasites, and involves multiple levels of host regulatory cells and cytokines; a breakdown of this regulation is observed in pathological disease. Currently, there is much interest in whether helminth-associated immune regulation may ameliorate allergy and autoimmunity, with investigations in both laboratory models and human trials. Understanding and exploiting the interactions between these parasites and the host regulatory network are therefore likely to highlight new strategies to control both infectious and immunological diseases.

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Section: Regulatory Cell Populations In Human Infectionmentioning

confidence: 99%

Helminth Infections and Host Immune Regulation

2012

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“…Several murine (5)(6)(7)(8)(9)(10)(11)(12) and human (13)(14)(15) studies showed that ongoing helminth infections induce the expansion of Foxp3 + Treg numbers. Depletion or functional inactivation of Tregs resulted in a reduced worm burden in some studies, suggesting that Treg induction promotes helminth survival by interference with the generation of a protective immune response (6,(16)(17)(18).…”

mentioning

confidence: 99%

Strongyloides ratti Infection Induces Expansion of Foxp3+ Regulatory T Cells That Interfere with Immune Response and Parasite Clearance in BALB/c Mice

Blankenhaus

Klemm

Eschbach

et al. 2011

The Journal of Immunology

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To escape expulsion by their host’s immune system, pathogenic nematodes exploit regulatory pathways that are intrinsic parts of the mammalian immune system, such as regulatory T cells (Tregs). Using depletion of Treg mice, we showed that Foxp3+ Treg numbers increased rapidly during infection with the nematode Strongyloides ratti. Transient depletion of Tregs during the first days of infection led to dramatically reduced worm burden and larval output, without aggravation of immune pathology. The transient absence of Tregs during primary infection did not interfere with the generation of protective memory. Depletion of Tregs at later time points of infection (i.e., day 4) did not improve resistance, suggesting that Tregs exert their counterregulatory function during the priming of S. ratti-specific immune responses. Improved resistance upon early Treg depletion was accompanied by accelerated and prolonged mast cell activation and increased production of types 1 and 2 cytokines. In contrast, the blockade of the regulatory receptor CTLA-4 specifically increased nematode-specific type 2 cytokine production. Despite this improved immune response, resistance to the infection was only marginally improved. Taken together, we provide evidence that Treg expansion during S. ratti infection suppresses the protective immune response to this pathogenic nematode and, thus, represents a mechanism of immune evasion.

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“…Recently, we reported a new role for granzymes in human helminth infection (11): gzmA/B expression in the local response to Onchocerca volvulus was associated with immunosuppression, Treg, and Ag release from treatment-induced dying filariae. Filarial nematodes like O. volvulus, Wuchereria, and Brugia spp.…”

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confidence: 99%

A Novel and Divergent Role of Granzyme A and B in Resistance to Helminth Infection

Hartmann

Marsland

Otto

et al. 2011

The Journal of Immunology

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Granzyme (gzm) A and B, proteases of NK cells and T killer cells, mediate cell death, but also cleave extracellular matrices, inactivate intracellular pathogens, and induce cytokines. Moreover, macrophages, Th2 cells, regulatory T cells, mast cells, and B cells can express gzms. We recently reported gzm induction in human filarial infection. In this study, we show that in rodent filarial infection with Litomosoides sigmodontis, worm loads were significantly reduced in gzmA×B and gzmB knockout mice during the whole course of infection, but enhanced only early in gzmA knockout compared with wild-type mice. GzmA/B deficiency was associated with a defense-promoting Th2 cytokine and Ab shift, enhanced early inflammatory gene expression, and a trend of reduced alternatively activated macrophage induction, whereas gzmA deficiency was linked with reduced inflammation and a trend toward increased alternatively activated macrophages. This suggests a novel and divergent role for gzms in helminth infection, with gzmA contributing to resistance and gzmB promoting susceptibility.

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Natural death of adult Onchocerca volvulus and filaricidal effects of doxycycline induce local FOXP3+/CD4+ regulatory T cells and granzyme expression

Cited by 36 publications

References 33 publications

Helminth Infections and Host Immune Regulation

Helminth Infections and Host Immune Regulation

Strongyloides ratti Infection Induces Expansion of Foxp3+ Regulatory T Cells That Interfere with Immune Response and Parasite Clearance in BALB/c Mice

A Novel and Divergent Role of Granzyme A and B in Resistance to Helminth Infection

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