IL-4–Producing Dendritic Cells Induced during <i>Schistosoma japonica</i> Infection Promote Th2 Cells via IL-4–Dependent Pathway

Ma, Yihan; Huang, Fengjuan; Li, Cong; Gong, Weiming; Bai, Hongmei; Li, Jun; Chen, Chunxia; Zhou, Nian-Yu; Jiang, Xiaoyu; Yin, Lan; Chen, Xiaoping

doi:10.4049/jimmunol.1403240

Cited by 21 publications

(25 citation statements)

References 36 publications

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“…Infection with helminth parasites elicits IL-4 production in mammalian hosts from a variety of cells313233, with T cells activated by helminth-educated DCs being a major source of the cytokine343536. For instance, mice infected with H. diminuta have increased synthesis of IL-43738, and the demonstration that adoptive transfer of HD-DCs promotes splenocyte production of IL-4 upon reactivation in vitro is in accordance with the data from use of the parasite.…”

Section: Discussionsupporting

confidence: 72%

Suppression of colitis by adoptive transfer of helminth antigen-treated dendritic cells requires interleukin-4 receptor-α signaling

Matisz

Faz-López

Thomson

et al. 2017

Sci Rep

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Infection with helminth parasites has been explored as a treatment for autoimmune and inflammatory diseases. As helminth antigens have potent immunomodulation properties capable of inducing regulatory programs in a variety of cell types, transferring cells treated with helminth antigens represents a novel extension to helminth therapy. Previous work determined that transfer of bone marrow-derived dendritic cells (DC) pulsed with a crude extract of the tapeworm Hymenolepis diminuta (HD) can suppress colitis in recipient mice. The present study explored the mechanism of disease suppression and the importance of interleukin (IL)-4 signaling. Transfer of HD-DCs suppressed dinitrobenzene sulfonic acid (DNBS)-induced colitis through activation of recipient IL-4 receptor-α. The transferred HD-DCs required IL-4Rα and the capacity to secrete IL-10 to drive IL-4 and IL-10 production and to suppress colitis in recipient mice. Treatment of DCs with IL-4 evokes an alternatively activated phenotype, but adoptive transfer of these cells did not affect the outcome of colitis. Collectively, these studies demonstrate the complexity between IL-4 and IL-10 in donor cells and recipient, and the requirement for parasite- and host-derived factors in this novel form of cell therapy. Thus IL-4Rα signaling is revealed as a pathway that could be exploited for helminth antigen cell-based therapy.

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Section: Discussionsupporting

confidence: 72%

Suppression of colitis by adoptive transfer of helminth antigen-treated dendritic cells requires interleukin-4 receptor-α signaling

Matisz

Faz-López

Thomson

et al. 2017

Sci Rep

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“…Beyond cytokine production, specialized innate immune cells drive the activation and polarization of adaptive immune responses mediated by T and B lymphocytes. During S. japonica infection, monocyte-derived dendritic cells (MDCs) produce IL-4 to trigger Th2 responses in the liver ( 9 ). These cells are commonly known as inflammatory DCs, characterized by the surface expression of CD11b + , CD11c + , MHC-II + , CD40 + , CD86 + , and Ly6C high ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

CD18 Regulates Monocyte Hematopoiesis and Promotes Resistance to Experimental Schistosomiasis

et al. 2018

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Infection with Schistosoma mansoni causes a chronic parasitic disease that progress to severe liver and gastrointestinal damage, and eventually death. During its development into mammalian hosts, immature schistosomula transit through the lung vasculature before they reach the liver to mature into adult worms. A low grade inflammatory reaction is induced during this process. However, molecules that are required for efficient leukocyte accumulation in the lungs of S. mansoni-infected subjects are unknown. In addition, specific leukocyte subsets that mediate pulmonary response during S. mansoni migration through the lung remain to be elucidated. β2 integrins are fundamental regulators of leukocyte trans-endothelial migration and function. Therefore, we investigated their role during experimental schistosomiasis. Mice that express low levels of CD18 (the common β2 integrin subunit) and wild type C57BL/6 mice were subcutaneously infected with S. mansoni cercariae. Cellular profiles of lungs and livers were evaluated in different time points after infection by flow cytometry. Low levels of CD18 affected the accumulation of patrolling Ly6Clow, intermediate Ly6Cinter monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells in the lungs 7 days after infection. This correlated with increased TNF-α levels. Strikingly, low CD18 expression resulted in monocytopenia both in the peripheral blood and bone marrow during acute infection. After 48 days, S. mansoni worm burdens were higher in the hepatic portal system of CD18low mice, which also displayed reduced hepatic accumulation of patrolling Ly6Clow and intermediate Ly6Cinter, but not inflammatory Ly6Chigh monocytes. Higher parasite burden resulted in increased granulomatous lesions in the liver, increased egg deposition and enhanced mortality. Overall, our data point for a fundamental role of CD18 for monocyte hematopoiesis during infection, which promotes an efficient host response against experimental schistosomiasis.

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“…IL4 has anti-in ammatory and in ammatory actions depending on context, and is able to promote release of IL10, as well as TGFβ regulatory cytokines [79]. IL4 is the most potent polarizing cytokine for Th2 differentiation, primarily produced by Th2 cells in the gut and by a subset of monocyte-derived in ammatory DCs [80]. Thus, elevated IL4 in DC-containing cultures could be a result of production by DCs, or, as the DCs were derived from human leukocytes and likely do not represent a pure population, by other leukocyte populations.…”

Section: Discussionmentioning

confidence: 99%

An In Vitro Intestinal Model Captures Immunomodulatory Properties of the Microbiota in Inflammation

Lock¹,

Caboni²,

Strandwitz³

et al. 2020

Preprint

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BackgroundThere is a growing appreciation for the significance of the gut microbiome in health and disease. Specifically, considerable effort has been put forth to understand mechanisms by which the microbiota modulates and responds to inflammation. Here, we explored whether oxidation metabolites produced by the host during inflammation, sodium nitrate and trimethylamine oxide, impact the composition of a human stool bacterial population in a gut simulator. We then assessed whether an immune-competent in vitro intestinal model responded differently to spent medium from bacteria exposed to these cues compared to spent medium from a control bacterial population. ResultsThe host-derived oxidation products were found to decrease levels of Bacteroidaceae and overall microbiota metabolic potential, while increasing levels of pro-inflammatory Enterobacteriaceae and lipopolysaccharide in bacterial cultures, reflecting shifts that occur in vivo in inflammation. Spent medium, with or without sodium nitrate and trimethylamine oxide, induced elevated intracellular mucin levels and reduced intestinal monolayer integrity as reflected in trans-epithelial electrical resistance relative to fresh medium controls. However, multiplexed cytokine analysis revealed markedly different cytokine signatures from intestinal cultures exposed to spent medium with added oxidation products relative to spent control medium, while cytokine signatures of cultures exposed to fresh media were similar regardless of addition of host-derived cues. Further, the presence of immune cells in the intestinal model was required for this differentiation of cytokine signatures. ConclusionsThis study indicates that simple in vitro immune-competent intestinal models can capture bacterial-mammalian cross-talk in response to host-derived oxidation products and supports utility of these systems for mechanistic studies of interactions between the gut microbiome and host in inflammation.

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IL-4–Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4–Dependent Pathway

Cited by 21 publications

References 36 publications

Suppression of colitis by adoptive transfer of helminth antigen-treated dendritic cells requires interleukin-4 receptor-α signaling

Suppression of colitis by adoptive transfer of helminth antigen-treated dendritic cells requires interleukin-4 receptor-α signaling

CD18 Regulates Monocyte Hematopoiesis and Promotes Resistance to Experimental Schistosomiasis

An In Vitro Intestinal Model Captures Immunomodulatory Properties of the Microbiota in Inflammation

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