Peripheral CD4 T Cells Rapidly Accumulate at the Host:Parasite Interface during an Inflammatory Th2 Memory Response

Morimoto, Motoko; Morimoto, Masahiro; Whitmire, Jeannette M.; Xiao, Shiyun; Anthony, Robert M.; Mirakami, Hiroshi; Star, Robert A.; Urban, Joseph F.; Gause, William C.

doi:10.4049/jimmunol.172.4.2424

Cited by 83 publications

(103 citation statements)

References 44 publications

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“…Alternatively activated macrophages, which are present in larger numbers than neutrophils, enclose the parasite and neutrophils forming a granulomatous structure. At the border of the granuloma there is an accumulation of CD4 + T cells, CD11c + dendritic cells (DCs) and eosinophils; however, basophils, mast cells, CD8 + T cells, γδT cells and B cells are absent 18,19,21 . Cytokine gene-expression analysis using laser capture microdissection has shown the development of a highly polarized T H 2-type response (high expression levels of IL-4 and IL-13, in the absence of IFNγexpression).…”

Section: Granuloma Formation In Helminth Infectionsmentioning

confidence: 99%

Protective immune mechanisms in helminth infection

et al. 2007

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Important insights have recently been gained in our understanding of how host immune responses mediate resistance to parasitic helminths and control associated pathological responses. Although similar cells and cytokines are evoked in response to infection by helminths as diverse as nematodes and schistosomes, the components of the response that mediate protection are dependent on the particular parasite. In this Review, we examine recent findings regarding the mechanisms of protection in helminth infections that have been elucidated in murine models and discuss the implications of these findings in terms of future therapies.More than two billion people are infected with parasitic helminths 1 . Although infections by these pathogens are generally not fatal, they are associated with high rates of morbidity, with chronic infection often leading to anaemia and malnourishment 1 . Developed countries have controlled these infections through primary health-care programmes and effective public sanitation, but helminth diseases are still widespread in developing nations and often drug treatment does not protect against rapid re-infection. The need for effective vaccines to control these infections is compelling and at least a few clinical trials are currently underway 2,3 ; however, one impediment towards development of an effective vaccine is a lack of understanding of the actual components of the immune response that mediate protection against helminths. In this Review, we examine the host protective mechanisms with regard to the cell types and molecules involved in helminth expulsion and in control of pathological inflammation that is associated with infection.Helminth infections and the corresponding host immune responses are products of a prolonged dynamic co-evolution between the host and parasite. For parasites, it is advantageous to trick the host into developing an ineffective immune response, to find a suitable niche for maturation and propagation, and to do so without killing or unduly harming the host. Conversely, the host NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript has to ideally generate an effective immune response to expel the parasite, and minimize its harmful effects, while not sacrificing its ability to effectively respond to other pathogens. The host immune system evolved in the context of a parasite-replete environment, and the balance of immune effector and regulatory cell populations are at least partly a consequence of ongoing responses to infectious organisms that can often simultaneously invade host tissues. Although such dynamic host-pathogen interactions exist throughout much of the world, in industrialized countries infectious diseases are better controlled as a result of increased hygiene, the administration of vaccines at an early age and the widespread use of antibiotics. Although this has resulted in marked reductions in chronic and severe disease, recent studies indicate a possible adverse effect of this enhanced control of infectious diseases that...

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Section: Granuloma Formation In Helminth Infectionsmentioning

confidence: 99%

Protective immune mechanisms in helminth infection

et al. 2007

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“…Total RNA was prepared from cells and reverse-transcribed, as previously described (30). For detection of IL-10 mRNA, real-time PCR commercial kits (Applied Biosystems) specific for IL-10 or rRNA were used, and all data were normalized to constitutive rRNA values.…”

Section: Analysis Of Gene Expression By Real-time Rt-pcrmentioning

confidence: 99%

Adenosine Augments IL-10 Production by Macrophages through an A2B Receptor-Mediated Posttranscriptional Mechanism

Németh¹,

Lutz²,

Csóka³

et al. 2005

The Journal of Immunology

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Adenosine receptor ligands have anti-inflammatory effects and modulate immune responses by up-regulating IL-10 production by immunostimulated macrophages. The adenosine receptor family comprises G protein-coupled heptahelical transmembrane receptors classified into four types: A1, A2A, A2B, and A3. Our understanding of the signaling mechanisms leading to enhanced IL-10 production following adenosine receptor occupancy on macrophages is limited. In this study, we demonstrate that adenosine receptor occupancy increases IL-10 production by LPS-stimulated macrophages without affecting IL-10 promoter activity and IL-10 mRNA levels, indicating a posttranscriptional mechanism. Transfection experiments with reporter constructs containing sequences corresponding to the AU-rich 3′-untranslated region (UTR) of IL-10 mRNA confirmed that adenosine receptor activation acts by relieving the translational repressive effect of the IL-10 3′-UTR. By contrast, adenosine receptor activation failed to liberate the translational arrest conferred by the 3′-UTR of TNF-α mRNA. The IL-10 3′-UTR formed specific complexes with proteins present in cytoplasmic extracts of RAW 264.7 cells. Adenosine enhanced binding of proteins to a region of the IL-10 3′-UTR containing the GUAUUUAUU nonamer. The stimulatory effect of adenosine on IL-10 production was mediated through the A2B receptor, because the order of potency of selective agonists was 5′-N-ethylcarboxamidoadenosine (NECA) > N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA) > 2-chloro-N6-cyclopentyladenosine (CCPA) = 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethyl-carboxamidoadenosine (CGS-21680). Also, the selective A2B antagonist, alloxazine, prevented the effect of adenosine. Collectively, these studies identify a novel pathway in which activation of a G protein-coupled receptor augments translation of an anti-inflammatory gene.

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“…Laser capture microdissection (LCM): LCM was performed as described previously [23,24]. Briefly, cryosectioned tissue was stained with HE and dehydrated, and LCM was performed with a PicCell II (Arcturus Engineering, Mountain View, CA, U.S.A.).…”

Section: Immunofluorescent Staining: Tissue Sections (4 M)mentioning

confidence: 99%

Orally Administered Rutin Inhibits the Gene Expression of Th2 Cytokines in the Gut and Lung in Aged Mice

Morimoto

Takagi

Higashi

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. Rutin is one of the flavonoids derived from plants such as buckwheat and is well known as a powerful antioxidant. To determine whether dietary rutin could modulate mucosal immunity, we examined the gene expression of Th1/Th2 cytokines and the receptors in the gut and lung. Aged (18 months old, 18 M) C3H/HeN female mice were orally administered rutin for 10 days. The small intestine and lung were taken and analyzed by real-time PCR for gene expression. Interleukin (IL)-13 and IL-13R2 gene expression was significantly low (P<0.05 respectively) in the small intestine of aged rutin-fed mice. Meanwhile, there was no change in interferon  gene expression between control and rutin-fed mice. IL-13 gene expression was also downregulated in the lung. To examine the mechanism of the inhibitory effect of rutin on Th2 cytokines in aged mice, intestinal nitric oxide synthase (NOS) expression was evaluated. Rutin inhibited inducible NOS (NOS2) gene expression, but not neuronal NOS and endothelial NOS. Gene analysis of cells collected from the small intestine by laser capture dissection revealed that NOS2 expression was significantly inhibited in crypt regions. Thus, rutin might be effective against a Th2-dominant profile through NOS2 inhibition in aged mice.

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Peripheral CD4 T Cells Rapidly Accumulate at the Host:Parasite Interface during an Inflammatory Th2 Memory Response

Cited by 83 publications

References 44 publications

Protective immune mechanisms in helminth infection

Protective immune mechanisms in helminth infection

Adenosine Augments IL-10 Production by Macrophages through an A2B Receptor-Mediated Posttranscriptional Mechanism

Orally Administered Rutin Inhibits the Gene Expression of Th2 Cytokines in the Gut and Lung in Aged Mice

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