Cytokine production by human polymorphonuclear leukocytes in response to different zygomycetes
Abstract number: P1356
Simitsopoulou M., Roilides E., Georgiadou E., Walsh T.J.
Objectives: Zygomycetes are opportunistic pathogens causing invasive infections with increased morbidity and mortality in immunocompromised patients. These infections are most frequently caused by Rhizopus oryzae (RO) and Rhizopus microsporus (RM). Infections caused by Cunninghamella bertholletiae (CB) are uncommon but severe. Laboratory animal studies have demonstrated that CB is more virulent than RO and RM in a pulmonary zygomycosis model. As polymorphonuclear leukocytes (PMNs) are critical components of antifungal host defence, we compared release of IL-6, IL-8 and TNF-a cytokines from human PMNs exposed to CB, RO, and RM.
Methods: 105 sporangiospores/ml of CB, RO and RM were incubated in RPMI at 37°C for 7, 9 and 9 h, respectively, in order to yield similar biomass ranging between 0.080.1 optical density as measured by spectrophotometry at 450 nm. PMNs isolated from healthy adult volunteers by dextran sedimentation/ficoll centrifugation were then added at effector:target (E:T) ratio of 10:1 or 20:1. The PMN-induced cytokine release of IL-6, IL-8 and TNF-a was assessed by ELISA quantitative assay after incubation of PMNs with hyphae for 1 h. Statistical analysis (n = 3) was performed using ANOVA with Dunnett post-test for multiple comparisons.
Results: See the table
CB induced decreased amounts of IL-8 release from PMNs compared to RO and RM (for both p < 0.05), but increased amounts of TNF-alpha release compared to RO and RM (for both p < 0.01). IL-6 was not expressed in PMNs exposed to the three zygomycetes after 1 h.
Conclusion: CB induces higher release of TNF-a and lower release of IL-8 in PMNs compared to RO and RM, while release of IL-6 remains unaffected. These findings provide insight into the possible mechanisms of increased resistance and severity of CB infections as compared to those of other zygomycetes.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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