Virus-associated activation of innate immunity induces rapid disruption of Peyer’s patches in mice

Heidegger, Simon; Anz, David; Stephan, Nicolas; Bohn, Bernadette; Herbst, Tina; Fendler, Wolfgang Peter; Suhartha, Nina; Sandholzer, Nadja; Kobold, Sebastian; Hotz, Christian; Eisenächer, Katharina; Radtke-Schuller, Susanne; Endres, Stefan; Bourquin, Carole

doi:10.1182/blood-2013-01-479311

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Journal article

Virus-associated activation of innate immunity induces rapid disruption of Peyer’s patches in mice

Heidegger, Simon Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Anz, David Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Stephan, Nicolas Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Bohn, Bernadette Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Herbst, Tina Chair of Pharmacology, Department of Medicine, University of Fribourg, Fribourg, Switzerland
Fendler, Wolfgang Peter Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Suhartha, Nina Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Sandholzer, Nadja Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Kobold, Sebastian Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Hotz, Christian Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Eisenächer, Katharina Medizinische Klinik, Klinikum Rechts der Isar, Technische Universitaet, Munich, Germany
Radtke-Schuller, Susanne Department Biology II, Ludwig-Maximilians-Universitaet, Munich, Germany
Endres, Stefan Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany
Bourquin, Carole Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitaet, Munich, Germany

03.07.2013

Published in:

Blood. - 2013, vol. 122, no. 15, p. 2591-2599

English Early in the course of infection, detection of pathogen-associated molecular patterns by innate immune receptors can shape the subsequent adaptive immune response. Here we investigate the influence of virus-associated innate immune activation on lymphocyte distribution in secondary lymphoid organs. We show for the first time that virus infection of mice induces rapid disruption of the Peyer's patches but not of other secondary lymphoid organs. The observed effect was not dependent on an active infectious process but due to innate immune activation and could be mimicked by virus-associated molecular patterns such as the synthetic double-stranded RNA poly(I:C). Profound histomorphological changes in Peyer's patches were associated with depletion of organ cellularity, most prominent among the B cell subset. We demonstrate that the disruption is entirely dependent on type I interferon. At the cellular level, we show that virus-associated immune activation by IFN-α blocks B-cell trafficking to the Peyer's patches by downregulating expression of the homing molecule α4β7-integrin. In summary, our data identify a mechanism that results in type I IFN-dependent rapid but reversible disruption of intestinal lymphoid organs during systemic viral immune activation. We propose that such re-routed lymphocyte trafficking may impact the development of B cell immunity to systemic viral pathogens.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language