Université de Fribourg

Hook length of the bacterial flagellum is optimized for maximal stability of the flagellar bundle

Spöring, Imke ; Martinez, Vincent A. ; Hotz, Christian ; Schwarz-Linek, Jana ; Grady, Keara L. ; Nava-Sedeño, Josué M. ; Vissers, Teun ; Singer, Hanna M. ; Rohde, Manfred ; Bourquin, Carole ; Hatzikirou, Haralampos ; Poon, Wilson C. K. ; Dufour, Yann S. ; Erhardt, Marc

In: PLOS Biology, 2018, vol. 16, no. 9, p. e2006989

Most bacteria swim in liquid environments by rotating one or several flagella. The long external filament of the flagellum is connected to a membrane-embedded basal body by a flexible universal joint, the hook, which allows the transmission of motor torque to the filament. The length of the hook is controlled on a nanometer scale by a sophisticated molecular ruler mechanism. However, why its...

Université de Fribourg

Engineered hybrid spider silk particles as delivery system for peptide vaccines

Lucke, Matthias ; Mottas, Inès ; Herbst, Tina ; Hotz, Christian ; Römer, Lin ; Schierling, Martina ; M.Herold, Heike ; Slotta, Ute ; Spinetti, Thibaud ; Scheibel, Thomas ; Winter, Gerhard ; Bourquin, Carole ; Engert, Julia

In: Biomaterials, 2018, vol. 172, p. 105–115

The generation of strong T-cell immunity is one of the main challenges for the development of successful vaccines against cancer and major infectious diseases. Here we have engineered spider silk particles as delivery system for a peptide-based vaccination that leads to effective priming of cytotoxic T-cells. The recombinant spider silk protein eADF4(C16) was fused to the antigenic peptide...

Université de Fribourg

TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function

Spinetti, Thibaud ; Spagnuolo, Lorenzo ; Mottas, Inès ; Secondini, Chiara ; Treinies, Marina ; Rüegg, Curzio ; Hotz, Christian ; Bourquin, Carole

In: OncoImmunology, 2016, vol. 5, no. 11, p. e1230578

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with the capacity to inhibit immunological responses. During cancer progression, MDSC are recruited to the tumor sites and secondary lymphoid organs, leading to the suppression of the antitumor function of NK and T cells. Here, we show that the TLR7/8 agonist resiquimod (R848) has a direct effect...

Université de Fribourg

Reprogramming of TLR7 signaling enhances antitumor NK and cytotoxic T cell responses

Hotz, Christian ; Treinies, Marina ; Mottas, Inès ; Rötzer, Laurin C. ; Oberson, Anne ; Spagnuolo, Lorenzo ; Perdicchio, Maurizio ; Spinetti, Thibaud ; Herbst, Tina ; Bourquin, Carole

In: OncoImmunology, 2016, vol. 5, no. 11, p. e1232219

Toll-like receptor (TLR) 7 agonists are effective in topical application for the immunotherapy of skin cancers, but their performance for the systemic treatment of solid tumors is limited by the development of TLR tolerance. In this study, we describe a novel strategy to overcome TLR tolerance and enhance TLR7-dependent antitumor immune responses through reprogramming of TLR signaling...

Université de Fribourg

TLR and RLR signaling are reprogrammed in opposite directions after detection of viral infection

Hotz, Christian ; Roetzer, Laurin C. ; Huber, Thomas ; Sailer, Andreas ; Oberson, Anne ; Treinies, Marina ; Heidegger, Simon ; Herbst, Tina ; Endres, Stefan ; Bourquin, Carole

In: The Journal of Immunology, 2015, vol. 195, no. 9, p. 4387–4395

Innate immune recognition of RNA is key for the initiation of immunity in response to viral infection. Although the factors controlling the detection of viral RNA by innate immune receptors in host cells are increasingly well understood, little is known about the dynamic changes in signaling after the initial triggering of these receptors. In this study, we report that preconditioning with the...

Université de Fribourg

Mycoplasma hyorhinis-contaminated cell lines activate primary innate immune cells via a protease-sensitive factor

Heidegger, Simon ; Jarosch, Alexander ; Schmickl, Martina ; Endres, Stefan ; Bourquin, Carole ; Hotz, Christian

In: PLoS ONE, 2015, vol. 10, no. 11, p. e0142523

Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR) function. In contrast, we show here that...

Université de Fribourg

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

In: Blood, 2013, p. -

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...

Université de Fribourg

TLR activation excludes circulating naive CD8+ T cells from gut-associated lymphoid organs in mice

Heidegger, Simon ; Kirchner, Sophie-Kathrin ; Stephan, Nicolas ; Bohn, Bernadette ; Suhartha, Nina ; Hotz, Christian ; Anz, David ; Sandholzer, Nadja ; Stecher, Bärbel ; Rüssmann, Holger ; Endres, Stefan ; Bourquin, Carole

In: The Journal of Immunology, 2013, vol. 190, no. 10, p. 5313–5320

The trafficking of effector T cells is tightly regulated by the expression of site-specific sets of homing molecules. In contrast, naive T cells are generally assumed to express a uniform pattern of homing molecules and to follow a random distribution within the blood and secondary lymphoid organs. In this study, we demonstrate that systemic infection fundamentally modifies the trafficking of...

Université de Fribourg

Systemic cancer immunotherapy with Toll-like receptor 7 agonists: Timing is everything

Hotz, Christian ; Bourquin, Carole

In: Oncoimmunology, 2012, vol. 1, no. 2, p. 227-228

Toll-like receptor (TLR) 7 agonists represent a promising strategy for the immunotherapy of cancer. We have recently investigated the influence of TLR tolerance on the efficacy of systemic tumor treatment with TLR7 ligands. We propose that considering the kinetics of receptor sensitivity highly improves the outcome of cancer immunotherapy.