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NLRP3 Controls the Development of Gastrointestinal CD11b+ Dendritic Cells in the Steady State and during Chronic Bacterial Infection


Arnold, Isabelle C; Zhang, Xiaozhou; Urban, Sabine; Artola-Borán, Mariela; Manz, Markus G; Ottemann, Karen M; Müller, Anne (2017). NLRP3 Controls the Development of Gastrointestinal CD11b+ Dendritic Cells in the Steady State and during Chronic Bacterial Infection. Cell Reports, 21(13):3860-3872.

Abstract

The gastric lamina propria is largely uncharted immunological territory. Here we describe the evolution and composition of the gastric, small intestinal, and colonic lamina propria mononuclear phagocyte system during the steady state and infection with the gastric pathogen Helicobacter pylori. We show that monocytes, CX3CR1hi macrophages, and CD11b+ dendritic cells are recruited to the infected stomach in a CCR2-dependent manner. All three populations, but not BATF3-dependent CD103+ DCs, sample red fluorescent protein (RFP)+Helicobacter pylori (H. pylori). Mice reconstituted with human hematopoietic stem cells recapitulate several features of the myeloid cell-H. pylori interaction. The differentiation in and/or recruitment to gastrointestinal, lung, and lymphoid tissues of CD11b+ DCs requires NLRP3, but not apoptosis-associated speck-like protein containing a carboxy-terminal CARD (ASC) or caspase-1, during steady-state and chronic infection. NLRP3-/- mice fail to generate Treg responses to H. pylori and control the infection more effectively than wild-type mice. The results demonstrate a non-canonical inflammasome-independent function of NLRP3 in DC development and immune regulation.

Abstract

The gastric lamina propria is largely uncharted immunological territory. Here we describe the evolution and composition of the gastric, small intestinal, and colonic lamina propria mononuclear phagocyte system during the steady state and infection with the gastric pathogen Helicobacter pylori. We show that monocytes, CX3CR1hi macrophages, and CD11b+ dendritic cells are recruited to the infected stomach in a CCR2-dependent manner. All three populations, but not BATF3-dependent CD103+ DCs, sample red fluorescent protein (RFP)+Helicobacter pylori (H. pylori). Mice reconstituted with human hematopoietic stem cells recapitulate several features of the myeloid cell-H. pylori interaction. The differentiation in and/or recruitment to gastrointestinal, lung, and lymphoid tissues of CD11b+ DCs requires NLRP3, but not apoptosis-associated speck-like protein containing a carboxy-terminal CARD (ASC) or caspase-1, during steady-state and chronic infection. NLRP3-/- mice fail to generate Treg responses to H. pylori and control the infection more effectively than wild-type mice. The results demonstrate a non-canonical inflammasome-independent function of NLRP3 in DC development and immune regulation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:26 December 2017
Deposited On:09 Jan 2018 15:39
Last Modified:28 Jun 2018 07:02
Publisher:Cell Press (Elsevier)
ISSN:2211-1247
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.celrep.2017.12.015
PubMed ID:29281833

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