Endogenous Interleukin (IL)–1α and IL‐1β Are Crucial for Host Defense against Disseminated Candidiasis
Interleukin (IL)-1 alpha and IL-1 beta are protective proinflammatory cytokines involved in host defense against Candida albicans. It is, however, unknown whether they provide protection through similar mechanisms. We investigated the effect of endogenous IL-1 alpha and IL-1 beta on disseminated C. albicans infection.
Mice deficient in the genes encoding IL-1 alpha (IL-1 alpha-/-), IL-1 beta (IL-1 beta-/-), or both molecules (IL-1 alpha-/- beta-/-) were used. Survival and C. albicans outgrowth in the kidneys was assessed after intravenous injection of C. albicans.
Both mortality and C. albicans outgrowth in the kidneys were significantly increased in IL-1 alpha-/- and IL-1 beta-/- mice, compared with those in control mice, with the IL-1 alpha-/- beta-/- mice being most susceptible to disseminated candidiasis. The host defense mechanisms triggered by IL-1 alpha and IL-1 beta differed from one another. IL-1 beta-/- mice showed decreased recruitment of granulocytes in response to an intraperitoneal C. albicans challenge, and generation of superoxide production was diminished in IL-1 beta-/- granulocytes. IL-1 alpha-/- mice had a reduced capacity to damage C. albicans pseudohyphae. Protective type 1 responses were deficient in both IL-1 alpha-/- and IL-1 beta-/- mice, as assessed by production of interferon-gamma by splenocytes in response to heat-killed C. albicans.
Although IL-1 alpha and IL-1 beta have differential effects on the various arms of host defense, both cytokines are essential for mounting a protective host response against invasive C. albicans infection.
Available from: Donna M MacCallum
- "The i.p. administration of Anakinra has physiological effects in the intestines at the doses used in our experiments (Meinzer et al., 2012). Despite its importance in systemic models (Vonk et al., 2006), blocking "
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ABSTRACT: The ability of Candida albicans to cause disease is associated with its capacity to undergo morphological transition between yeast and filamentous forms, but the role of morphology in colonisation and dissemination from the gastrointestinal (GI) tract remains poorly defined. To explore this, we made use of wild type and morphological mutants of C. albicans in an established model of GI tract colonization, induced following antibiotic-treatment of mice. Our data reveal that GI tract colonization favours the yeast form of C. albicans, that there is constitutive low level systemic dissemination in colonized mice that occurs irrespective of fungal morphology, and that colonization is not controlled by Th17 immunity in otherwise immunocompetent animals. These data provide new insights into the mechanisms of pathogenesis and commensalism of C. albicans, and have implications for our understanding of human disease.
Cellular Microbiology 10/2014; 17(4). DOI:10.1111/cmi.12388 · 4.92 Impact Factor
Available from: Abdelhabib Semlali
- "Indeed, when comparing Figure 9(a) related to the cell growth and Figure 9(b) related to IL-1β secretion, a reverse image can be seen, where the lower number of viable fibroblasts corresponds to a high level of IL-1β secretion. The importance of IL-1β in protecting the mammalian host from invasive C. albicans infection has been clearly demonstrated, as mice deficient in IL-1β experienced decreased survival levels and increased fungal burdens relative to wild-type mice [54, 55]. The presence of CSC may thus contribute to the interaction of C. albicans with human gingival fibroblasts, leading to fibroblast stimulation and IL-1β secretion to overcome the damaging effect of CSC and C. albicans, as the C. albicans untreated with CSC led to low level of IL-1β secretion by the fibroblasts. "
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ABSTRACT: The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC) on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P < 0.01) sensitive to oxidation but significantly (P < 0.01) resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P < 0.01) slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers.
BioMed Research International 09/2014; 2014:963156. DOI:10.1155/2014/963156 · 2.71 Impact Factor
Available from: Francis Vasseur
- "Assembly of inflammasome proteins enables activation of caspase 1 and, thereby, initiates the second danger signal leading to the cleavage of the inflammatory cytokine IL-1β into its biologically active form. IL-1β is involved in animal models of fungal infection, together with IL1-α and IL-18 [21-25]. However, there are now strong evidences that it has a significant role in modulating the adaptive immune response [26,27]. "
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Crohn’s disease (CD) is associated with elevated anti-glycans antibody response in 60% of CD patients, and 25% of healthy first-degree relatives (HFDRs), suggesting a genetic influence for this humoral response. In mice, anti-glucan antibody response depends on the NLRP3 inflammasome. Here, we explored the effect of mutated CARD8, a component of the inflammasome, on anti-glycans antibody response in human.
The association between p.C10X mutation (rs2043211) of the CARD8 gene and the levels of anti-glycans antibody response was examined in 39 CD families. The family-based QTDT association test was used to test for the genetic association between CARD8 p.C10X mutation and anti-glycan antibodies in the pedigrees. The difference in antibody responses determined by ELISA was tested in a subgroup of CD probands (one per family) and in a subgroup of HFDRs using the Wilcoxon Kruskal Wallis non-parametric test.
The QTDT familial transmission tests showed that the p.C10X mutation of CARD8 was significantly associated with lower levels of antibody to mannans and glucans but not chitin (p=0.024, p=0.0028 and p=0.577, for ASCA, ALCA and ACCA, respectively). These associations were independent of NOD2 and NOD1 genetic backgrounds. The p.C10X mutation significantly associated or displayed a trend toward lower ASCA and ALCA levels (p=0.038 and p=0.08, respectively) only in the subgroup of CD probands. Such associations were not significant for ACCA levels in both subgroups of CD probands and of HFDRs.
Our results show that ASCA and ALCA but not ACCA levels are under the influence of CARD8 genotype. Alteration of CARD8, a component of inflammasome, is associated with lower levels of antibodies directed to mannans and glucans at least in CD patients.
BMC Medical Genetics 03/2013; 14(1):35. DOI:10.1186/1471-2350-14-35 · 2.08 Impact Factor
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