The Journal of immunology : official journal of the American Association of Immunologists
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MicroRNAs (miRNAs) are short noncoding RNAs that regulate a broad spectrum of biological processes, including immune responses. Although the contributions of miRNAs to the function of immune cells are beginning to emerge, their specific roles remain largely unknown. IL-33 plays an important role in macrophage activation for innate host defense and proinflammatory responses. ⋯ Treatment with a specific inhibitor of miR-487b function also resulted in increased levels of IL-33 mRNA, which augmented LPS-induced expression of these inflammatory mediators in macrophages. Collectively, our results indicate that miR-487b plays a negative regulatory role in macrophages by controlling the levels of IL-33 transcript and protein to fine-tune innate immune host defense and proinflammatory responses of these cells. Thus, miR-487b plays an important role in the regulation of macrophage homeostasis and activation by targeting IL-33 transcripts.
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Immune recognition of pathogen-associated ligands leads to assembly and activation of inflammasomes, resulting in the secretion of inflammatory cytokines IL-1β and IL-18 and an inflammatory cell death called pyroptosis. Inflammasomes are important for protection against many pathogens, but their role during chronic infectious disease is poorly understood. Pseudomonas aeruginosa is an opportunistic pathogen that persists in the lungs of cystic fibrosis (CF) patients and may be responsible for the repeated episodes of pulmonary exacerbation characteristic of CF. ⋯ P. aeruginosa isolates from CF patients failed to induce inflammasome activation, as measured by the secretion of IL-1β and IL-18 and by pyroptotic cell death, during both stable infection and exacerbation. Inflammasome evasion likely was due to reduced expression of inflammasome ligands and reduced motility and was not observed in environmental isolates or isolates from acute, non-CF infection. These results reveal a novel mechanism of pathogen adaptation by P. aeruginosa to avoid detection by inflammasomes in CF patients and indicate that P. aeruginosa-activated inflammasomes are not involved in CF pulmonary exacerbations.