Lack of antigen-specific Th1 response alters granuloma formation and composition inSchistosoma mansoni-infected MyD88-/- mice

Layland, Laura E.; Wagner, Hermann; Costa, Clarissa U. Prazeres da

doi:10.1002/eji.200526273

Cited by 50 publications

(58 citation statements)

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“…Sterile SEA was prepared according to standard procedures (2). Digestion of SEA was carried out with 200 μg/mL proteinase K (Qiagen) for 1 h at 56°C.…”

Section: Methodsmentioning

confidence: 99%

“…Sections (4 μm) were stained with Masson blue and examined microscopically (Axioskop; Zeiss) for qualitative and quantitative alterations. The sizes of individual granulomas were determined by measuring the diameters to calculate the size of spherical granulomas (2). To determine the parasite burden, pieces of weighed liver and intestine samples from individual mice were digested in 4% KOH (Roth) at 37°C for 4 h. After centrifugation, the released eggs were microscopically counted.…”

Section: Methodsmentioning

confidence: 99%

“…The morbidity in Schistosoma mansoni infection arises from the granulomatous, CD4 + T cell-mediated response to eggs that become trapped in the liver and intestinal tissues (1,2). Immunologically, the S. mansoni infection is dominated by two distinct Th phases: an initial Th1 (IFN-γ) response which then switches to a stronger Th2 (IL-10, IL-5, IL-13) status (3,4).…”

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confidence: 99%

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Schistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses

Ritter

Groß

Kays

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

218

204

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The propensity of helminths, such as schistosomes, to immunomodulate the host's immune system is an essential aspect of their survival. Previous research has demonstrated how soluble schistosomal egg antigens (SEA) dampen TLR-signaling during innate immune responses. We show here that the suppressive effect by SEA on TLR signaling is simultaneously coupled to the activation of the Nlrp3 (NLR family, pyrin domain containing 3) inflammasome and thus IL-1β production. Therefore, the responsible protein component of SEA contains the second signal that is required to trigger proteolytic pro-IL-1β processing. Moreover, the SEA component binds to the Dectin-2/FcRγ (Fc receptor γ chain) complex and activates the Syk kinase signaling pathway to induce reactive oxygen species and potassium efflux. As IL-1β has been shown to be an essential orchestrator against several pathogens we studied the in vivo consequences of Schistosoma mansoni infection in mice deficient in the central inflammasome adapter ASC and Nlrp3 molecule. These mice failed to induce local IL-1β levels in the liver and showed decreased immunopathology. Interestingly, antigen-specific Th1, Th2, and Th17 responses were down-regulated. Overall, these data imply that component(s) within SEA induce IL-1β production and unravel a crucial role of Nlrp3 during S. mansoni infection.

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“…Sterile SEA was prepared according to standard procedures (2). Digestion of SEA was carried out with 200 μg/mL proteinase K (Qiagen) for 1 h at 56°C.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Schistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses

Ritter

Groß

Kays

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

218

204

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“…As a matter of fact, a sepsis-like situation often occurs during the acute phase of protozoan parasite infection, including infection with Trypanosoma, Toxoplasma, Plasmodium and Leishmania species, given the overwhelming presence of parasites/TLR ligands and the ensuing massive inflammatory/Th1 (IFN-g) responses [37,38]. It should be noted that helminth parasites, such as S. mansoni, also trigger TLR/MyD88 signaling to induce an early Th1 response, which is subsequently converted to a dominant Th2 response [39,40]. Remarkably, CTL-suppressive CD11b small mononuclear cells significantly increased in different tissues after S. mansoni infection in mice and concentrated in the liver around dilated blood vessels and at the edge of granulomas.…”

Section: Factors Mediating Mdsc Induction During Parasitic Infectionsmentioning

confidence: 99%

Myeloid‐derived suppressor cells in parasitic infections

et al. 2010

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BelgiumMyeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that share a common property of suppressing immune responses. Several helminth and protozoan parasite species have developed efficient strategies to increase the rate of medullary or extramedullary myelopoiesis and to induce the expansion and accumulation of immature myeloid cells such as MDSC. In this review, we examine current knowledge on the factors mediating enhanced myelopoiesis and MDSC induction and recruitment during parasitic infections and how the MDSC phenotype and mechanism of immune modulation and suppression depends on the factors they encounter within the host. Finally, we place MDSC expansion in the context of the critical balance between parasite elimination and pathogenicity to the host and suggest attractive avenues for future research.Key words: Myeloid-derived suppressor cells . Myelopoiesis . Parasitic infection .T-cell suppression IntroductionParasitic infections are notoriously associated with suppression of immune responses. Populations of mature myeloid cells, such as macrophages in various activation states, are capable of displaying immunosuppressive features, and as a result play important roles in the critical balance between parasite elimination and pathogenicity to host tissues [1][2][3]. Heterogeneous populations of immature myeloid cells, characterized by the surface expression of both Gr-1 and CD11b molecules in mice and a shared potent immune-suppressing activity in vitro and in vivo, have been recognized to arise as a conserved response to various insults, including cancer, bacterial and parasitic infections. Collectively, these cells have been termed myeloid-derived suppressor cells (MDSC) [4]. A number of factors complicate the analysis of MDSC biology. First, MDSC are a heterogeneous mixture of immature myeloid cells that are in various intermediate stages of myeloid cell differentiation (reflected by expression of various levels of macrophage and DC markers such as F4/80 and CD11c, respectively, as well as MHC class II, CD80/86) and murine MDSC consist of different subpopulations with varying levels of reactivity with the Gr-1 monoclonal antibody. This Gr-1 antibody binds a common epitope on the Ly6G and Ly6C antigens [5]. Using antibodies specifically recognizing Ly6C or Ly6G, MDSC have been shown to contain at least two main subfractions: the CD11b suppressive capacity in all tumor models [7,16]. The heterogeneity and plasticity of MDSC and the lack of markers to optimally distinguish MDSC from other, more mature myeloid cell types, render T-cell anti-proliferative activity to be the ultimate defining characteristic of MDSC. Despite the above-mentioned limitations, the impact of MDSC on immune responses has made MDSC the topic of intense research. To date, most of the attention has been focused on cancer-associated MDSC, whereas relatively few studies have reported the activation, phenotype and especially the role of MDSC during parasitic infections (Table 1). In thi...

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“…La forte toxicité des protéines granulaires des éosinophiles ne s'exerce pas uniquement contre les parasites helminthes mais cause aussi des dommages tissulaires chez l'hôte. Dans des souris dépourvues de Myd88 -une molécule adaptatrice intervenant dans les voies de signalisation en aval de certains TLR -infectées par S. mansoni 1 , même si aucune différence n'a été observée en ce qui concerne la mortalité, le taux d'immunoglobulines IgE ou la charge parasitaire, la taille du granulome hépatique était néanmoins réduite ainsi que la taille de l'infiltrat à éosinophiles [23]. Une possible interprétation de ces données serait que l'absence de signalisation TLR dans ces éosinophiles Myd88 -/-compromette leur recrutement via certains antigènes parasitaires qui sont des ligands naturels de ces récepteurs.…”

Section: éOsinophiles Et Infectionsunclassified