Stefan A. Fattinger

Strong, sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility

Stefan A. Fattinger, Bianca Parisi, Roberto A. Chavez, Marian R. Fairgrieve et autres

Mycobacterium tuberculosis (Mtb) causes over one million deaths annually, but most infected individuals never exhibit symptoms. Type I interferons (IFNs) have emerged as a major factor driving susceptibility to Mtb, but how type I IFNs impair immunity to Mtb is a key …

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TTSS-2 virulence drives inflammatory destruction of the gut epithelial barrier and modulates inflammatory response profiles in the Salmonella-infected mouse gut

Ursina Enz, Ersin Gül, Luca Maurer, Kamilė Čerepenkaitė et autres

Salmonella enterica serovar Typhimurium (S. Tm) employs type III secretion system 1 and 2 (TTSS-1 and TTSS-2) to infect host tissues. In orogastric infections, both TTSSs manipulate host responses, increasing mucosal pathogen loads and eliciting inflammation. However, we still do not fully …

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TTSS-2 virulence drives inflammatory destruction of the gut epithelial barrier and modulates inflammatory response profiles in the Salmonella-infected mouse gut

Ursina Enz, Ersin Gül, Luca Maurer, Kamilė Čerepenkaitė et autres

Salmonella enterica serovar Typhimurium (S. Tm) employs type III secretion system 1 and 2 (TTSS-1 and TTSS-2) to infect host tissues. In orogastric infections, both TTSSs manipulate host responses, increasing mucosal pathogen loads and eliciting inflammation. However, we still do not fully …

NAIP/NLRC4 inflammasome dynamics in murine enteroids are tuned by NAIP ligand concentration and epithelial cell differentiation

Patrick Rosendahl Andreassen, Chantal Ernst, Marisa Pimentel Mendes, Thea Bill Andersen et autres

Inflammasomes are central components of mammalian innate immunity activated upon the detection of danger signals such as pathogen ligands. This activation generally leads to pyroptosis and interleukin release, but specific responses vary between cell types. Here, we study nucleotide-binding, leucine-rich repeat (NLR) …

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SP140–RESIST pathway regulates interferon mRNA stability and antiviral immunity

Kristen C. Witt, Adam Dziulko, Joohyun An, Filip Pekovic et autres

Abstract Type I interferons are essential for antiviral immunity 1 but must be tightly regulated 2 . The conserved transcriptional repressor SP140 inhibits interferon-β ( Ifnb1 ) expression through an unknown mechanism 3,4 . Here we report that SP140 does not directly …

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Vaccine-enhanced competition permits rational bacterial strain replacement in the gut

Verena Lentsch, Aurore Woller, Andrea Rocker, Selma Aslani et autres

Colonization of the intestinal lumen precedes invasive infection for a wide range of enteropathogenic and opportunistic pathogenic bacteria. We show that combining oral vaccination with engineered or selected niche-competitor strains permits pathogen exclusion and strain replacement in the mouse gut lumen. This …

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The SP140-RESIST pathway regulates interferon mRNA stability and antiviral immunity

Kristen C. Witt, Adam Dziulko, Joohyun An, Filip Pekovic et autres

Abstract Type I interferons (IFN-Is) are essential for antiviral immunity but must be tightly regulated 1–3 . The conserved transcriptional repressor SP140 inhibits interferon beta ( Ifnb1 ) expression via an unknown mechanism 4,5 . Here we report that SP140 does not …

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Direct Salmonella injection into enteroid cells allows the study of host–pathogen interactions in the cytosol with high spatiotemporal resolution

Chantal Ernst, Patrick Rosendahl Andreassen, Gabriel H. Giger, Bidong D. Nguyen et autres

Intestinal epithelial cells (IECs) play pivotal roles in nutrient uptake and in the protection against gut microorganisms. However, certain enteric pathogens, such as Salmonella enterica serovar Typhimurium (S. Tm), can invade IECs by employing flagella and type III secretion systems (T3SSs) with …

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Early cellular mechanisms of type I interferon-driven susceptibility to tuberculosis

Dmitri Ivanovich Kotov, Ophelia Vosshall Lee, Stefan A. Fattinger, Charlotte A. Langner et autres

Mycobacterium tuberculosis (Mtb) causes 1.6 million deaths annually. Active tuberculosis correlates with a neutrophil-driven type I interferon (IFN) signature, but the cellular mechanisms underlying tuberculosis pathogenesis remain poorly understood. We found that interstitial macrophages (IMs) and plasmacytoid dendritic cells (pDCs) are dominant …

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Gasdermin D is the only Gasdermin that provides protection against acute Salmonella gut infection in mice

Stefan A. Fattinger, Luca Maurer, Petra Geiser, Elliott M. Bernard et autres

Gasdermins (GSDMs) share a common functional domain structure and are best known for their capacity to form membrane pores. These pores are hallmarks of a specific form of cell death called pyroptosis and mediate the secretion of pro-inflammatory cytokines such as interleukin …

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The microbiota conditions a gut milieu that selects for wild-type Salmonella Typhimurium virulence

Ersin Gül, Erik Bakkeren, Guillem Salazar, Yves Steiger et autres

Salmonella Typhimurium elicits gut inflammation by the costly expression of HilD-controlled virulence factors. This inflammation alleviates colonization resistance (CR) mediated by the microbiota and thereby promotes pathogen blooms. However, the inflamed gut-milieu can also select for hilD mutants, which cannot elicit or …

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Epithelial inflammasomes, gasdermins, and mucosal inflammation – Lessons from Salmonella and Shigella infected mice

Ersin Gül, Stefan A. Fattinger, Mikael E. Sellin, Wolf‐Dietrich Hardt

Besides its crucial function in nutrient absorbance and as barrier against the microbiota, the gut epithelium is essential for sensing pathogenic insults and mounting of an appropriate early immune response. In mice, the activation of the canonical NAIP/NLRC4 inflammasome is critical for …

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