Distinct sequential death complexes regulate pyroptosis and IL-1β release in response to blockade of immune signaling.

Pathogen infection of host cells triggers an inflammatory cell death termed pyroptosis via activation of inflammatory caspases. However, blockade of immune signaling kinases by the virulence factor YopJ triggers cell death involving both apoptotic caspase-8 and pyroptotic caspase-1. While caspase-1 is normally activated within inflammasomes, -induced caspase-1 activation is independent of known inflammasome components.

A TNF-IL-1 circuit controls Yersinia within intestinal pyogranulomas.

Tumor necrosis factor (TNF) is a pleiotropic inflammatory cytokine that mediates antimicrobial defense and granuloma formation in response to infection by numerous pathogens. We previously reported that Yersinia pseudotuberculosis colonizes the intestinal mucosa and induces the recruitment of neutrophils and inflammatory monocytes into organized immune structures termed pyogranulomas (PG) that control Yersinia infection. Inflammatory monocytes are essential for the control and clearance of Yersinia within intestinal PG, but how monocytes mediate Yersinia restriction is poorly understood.

A TNF-IL-1 circuit controls within intestinal granulomas.

Tumor necrosis factor (TNF) is a pleiotropic inflammatory cytokine that mediates antimicrobial defense and granuloma formation in response to infection by numerous pathogens. colonizes the intestinal mucosa and induces recruitment of neutrophils and inflammatory monocytes into organized immune structures termed pyogranulomas that control the bacterial infection. Inflammatory monocytes are essential for control and clearance of within intestinal pyogranulomas, but how monocytes mediate restriction is poorly understood.

Inflammatory monocytes promote granuloma control of Yersinia infection.

Granulomas are organized immune cell aggregates formed in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis (Yp) blocks innate inflammatory signalling and immune defence, inducing neutrophil-rich pyogranulomas (PGs) within lymphoid tissues. Here we uncover that Yp also triggers PG formation within the murine intestinal mucosa.

Minor alterations in the intestinal microbiota composition upon Rotavirus infection do not affect susceptibility to DSS colitis.

Viral triggers at the intestinal mucosa can have multiple global effects on intestinal integrity, causing elevated intestinal barrier strength and relative protection from subsequent inflammatory bowel disease (IBD) induction in various models. As viruses can interfere with the intestinal immune system both directly and indirectly through commensal bacteria, cause-effect relationships are difficult to define. Due to the complexity of putatively causative factors, our understanding of such virus-mediated protection is currently very limited.

Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation.

RIPK1 regulates cell death and inflammation through kinase-dependent and -independent mechanisms. As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities.

HVEM LIGHTs the Way for ILC3s.

The early response to bacterial infection requires cytokine responses by immune cells. In this issue of Cell Host & Microbe, Seo et al. (2018) demonstrate that TNF-TNFR superfamily molecules LIGHT and HVEM stimulate early IFN-γ production by type 3 innate lymphoid cells, which are critical for defense against Yersinia enterocolitica.

Eosinophils are key regulators of perivascular adipose tissue and vascular functionality.

Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function.

Acute infection with the intestinal parasite Trichuris muris has long-term consequences on mucosal mast cell homeostasis and epithelial integrity.

A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-intestinal epithelium following infection with the nematode Trichuris muris and persisted at this site for several months after worm expulsion. Mast cell accumulation in the epithelium was associated with the induction of type-2 immunity and appeared to be driven by increased maturation of local progenitors in the intestinal lamina propria.

Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli.

The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes.