1,720,985 research outputs found
A Role for Yeast/Pseudohyphal Cells of Candida albicans in the Correlated Expression of NLRP3 Inflammasome Inducers in Women With Acute Vulvovaginal Candidiasis
No full textPeptides derived from the proteolysis of serum proteins and immunoglobulins induce IL-1beta production independently of inflammasome activation
No full textGILZ restrains neutrophil activation by inhibiting the MAPK pathway
No full textGlucocorticoid-induced leucine zipper (GILZ) exerts anti-inflammatory effects on the immune cells. However, less is known about GILZ function in neutrophils. We aimed to define the specific role of GILZ in basal neutrophil activity during an inflammatory response. GILZ knockdown resulted in a persistent activation state of neutrophils, as evidenced by increased phagocytosis, killing activity, and oxidative burst in GILZ-knockout (KO) neutrophils. This enhanced response caused severe disease in a dinitrobenzene sulfonic acid (DNBS)-induced colitis model, where GILZ-KO mice had prominent granulocytic infiltrate and excessive inflammatory state. We used a Candida albicans intraperitoneal infection model to unravel the intracellular pathways affected by GILZ expression in activated neutrophils. GILZ-KO neutrophils had stronger ability to clear the infectious agent than the wild-type (WT) neutrophils, and there was more activation of the NOX2 (NADPH oxidase 2) and p47phox proteins, which are directly involved in oxidative burst. Similarly, the MAPK pathway components, that is, ERK and p38, which are involved in the oxidative burst pathway, were highly phosphorylated in GILZ-KO neutrophils. Evaluation of GILZ expression kinetics during C. albicans infection revealed down-regulation that correlated inversely with the state of neutrophil activation, which was evaluated as oxidative burst. Overall, our findings define GILZ as a regulator of neutrophil functions, as its expression contributes to limiting neutrophil activation by reducing the activation of the signaling pathways that control the basal neutrophil functions. Controlling GILZ expression could help regulate a continuous inflammatory state that can result in chronic inflammatory and autoimmune diseases
Inflammatory response during human vaginal infection with Candida albicans
No full textIntroduction. The microbiological, pathological and clinical factors determining vaginal candidiasis and recurrent vaginal candidiasis have long been studied, particularly using rodent models. The validity of which for understanding the pathogenesis of disease in women has been questioned. The most prevalent agent is critically determined by activation of microbial and host factors leading to persistent vaginal inflammation coupled to the inability of the inflammatory cells to resolve the fungal infection. Here we studied the activation of inflammasome complex neutrophil-recruiting and activating cytokines in the vaginal secretion of women with clinically established vaginal candidiasis.
Materials and methods. In human vaginal samples positive for C. albicans with vaginal candidiasis (n=20) and carriage (n=15), infiltration of neutrophils, inflammatory mediators such as IL-8 and IL-1β, activation of inflammasome complex and expression of aspartyl proteases (SAPs) were examined.
Results. In vaginal swabs of patients with vaginal candidiasis we found: i) consistent recruitment of neutrophils; ii) appreciable level of IL-8 and IL-1β; iii) activation of inflammasome complex; iv) consistent expression of SAP2, SAP5 and SAP6.
Conclusions. These results show that immunopathogenesis of vaginal candidiasis is mediated by local recruitment of neutrophils, inflammatory cytokines secretion and inflammasome activation that mirror the upregulation of SAP2, SAP5 and SAP6 gene expression
Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues
Full text linkIn this study, an initial in vivo evaluation of a new amikacin-deoxycholate hydrophobic salt aimed at potentiating amikacin action against hard-to-treat lung infections was undertaken by quantifying, for the first time, amikacin in whole blood. Pharmacokinetic evaluation after intranasal administration in a murine model showed higher drug retention in the lungs compared to blood, with no significant differences between the salt and the free drug. Upon repeated administrations, the two treatments resulted in nonsignificant tissue damage and mild higher inflammation for the hydrophobic salt. Whole-blood analysis highlighted an unreported high partition of amikacin in blood components up to 48 h, while significant lung levels were measured up to 72 h. Such a new observation was considered responsible for the nearly overlapping pharmacokinetic profiles of the two treatments. To overcome such an issue, a dry powder in an inhalable form may be best suited. Moreover, if confirmed in humans, and considering the current once-a-day regimen for amikacin aerosols, important yet-to-be-explored clinical implications may be postulated for such amikacin persistence in the organism
A role for secretory aspartyl proteinases of Candida albicans in mouse vaginal inflammation and vaginal candidiasis
No full textApoptosis of vaginal epithelial cells in clinical samples from women with diagnosed bacterial vaginosis
Full text linkAspartyl proteinases of Candida albicans induce caspase-11: implication in promoting inflammatory response.
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In vivo induction of neutrophils chemotaxis by secretory aspartyl proteinases of Candida albicans
Full text linkSecretory aspartyl proteinases (Saps) of Candida albicans are key virulence traits which cause inflammasome-dependent, aseptic inflammation in a mouse model of vaginitis. In this paper, neutrophil migration in response to Sap2, Sap6 and chemo-attractive products released from Sap-treated vaginal epithelium was measured in vitro, ex vivo and in vivo. Our results show that Sap2 and Sap6 induce neutrophil migration and production of potent chemoattractive chemokines such as IL-8 and MIP-2 by vaginal epithelial cells. Our data suggest that at least part of MIP-2 production depends upon IL-1β activity. The vaginal fluid of Candida-infected mice contained a heat-labile inhibitor of neutrophil candidacidal activity that was absent from the vaginal fluid of Sap-treated mice. Overall, our data provide additional information on the capacity of C. albicans Saps to cause aseptic vaginal inflammation and highlight the potential role of some chemokines released from vaginal epithelial cells in this phenomenon
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