Macrophage migration inhibitory factor (MIF) exerts multiple effects on immune cells, as well as having functions outside the immune system. MIF can promote inflammation through the induction of other cytokines, including TNF, IL-6, and IL-1 family cytokines. Here, we show that inhibition of MIF regulates the release of IL-1α, IL-1β, and IL-18, not by affecting transcription or translation of these cytokines, but via activation of the NLRP3 inflammasome. MIF is required for the interaction between NLRP3 and the intermediate filament protein vimentin, which is critical for NLRP3 activation. Further, we demonstrate that MIF interacts with NLRP3, indicating a role for MIF in inflammasome activation independent of its role as a cytokine. These data advance our understanding of how MIF regulates inflammation and identify it as a factor critical for NLRP3 inflammasome activation.

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Helicobacter pylori is a Gram-negative pathogen that colonizes the gastric epithelium of 50-60% of the world's population. Approximately one-fifth of the infected individuals manifest severe diseases such as peptic ulcers or gastric cancer. H. pylori infection has proven difficult to cure despite intensive antibiotic treatment. One possible reason for the relatively high resistance to antimicrobial therapy is the ability of H. pylori to reside inside host cells. Although considered by most as an extracellular pathogen, H. pylori can invade both gastric epithelial cells and immunocytes to some extent. The intracellular survival of H. pylori has been implicated in its ability to persist in the stomach, evade host immune responses and resist eradication by membrane-impermeable antibiotics. Interestingly, recent evidence suggests that macroautophagy, a cellular self-degradation process characterized by the formation of double-membraned autophagosomes, plays an important role in determining the intracellular fate of H. pylori. Detailed understanding of the interaction between H. pylori and host cell autophagic processes is anticipated to provide novel insights into the molecular mechanisms of macroautophagy and H. pylori pathogenesis, opening new avenues for the therapeutic intervention of autophagy-related and H. pylori-related disorders. The impact of autophagic processes on the intracellular fate of Helicobacter pyloriMore tricks from an enigmatic pathogen?

In macrophages, H. pylori infection does not induce LAP, but can induce canonical autophagy, which entraps a very small fraction of intracellular bacteria. We propose that this subpopulation of intracellular H. pylori might have escaped from phagosomes into the cytosol before being sequestered by autophagosomes. The cagPAI of H. pylori has only minor influence, if any, on the extent of these processes.

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