Abstract
Objective Candida glabrata (C. glabrata) causes infections associated with severe sepsis and high mortality. This study describes the effects of micafungin (MCF), itraconazole (ICZ), and amphotericin B (AmB) on the function of macrophages during C. glabrata infection. Methods RAW264.1 macrophages were treated with MCF, ICZ, or AmB and then challenged with C. glabrata. Cytokines from infected macrophage supernatants and the levels of superoxide dismutase (SOD) in macrophages were measured at different time points after phagocytosis. Results The activity of SOD was significantly increased in RAW264.1 cells that phagocytized C. glabrata and reached a peak level at 6 hours (P < 0.05). ICZ and AmB did not affect the SOD activity in cells that phagocytized C. glabrata versus that in untreated macrophage. C. glabrata stimulated macrophages to secrete cytokines. Neither ICZ nor AmB affected the secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), or tumor necrosis factor-α (TNF-α) by C. glabrata-infected macrophages. However, MCF downregulated the secretion of TNF-α by infected macrophages and reduced the SOD activity of C. glabrata compared with those in untreated controls. Conclusion Echinocandins may increase their antifungal efficacy by altering the innate immune response of macrophages and attenuating antioxidants of this organism.
Highlights
Candida is generally regarded as a nonpathogenic symbiotic microbe of human mucosal tissue that occasionally causes opportunistic infections
The success of azole antifungal agents for the control of fungal infection has been consistent with the increase in non-Candida albicans (C. albicans) infection, among which C. glabrata infection has increased by three times
Contrary to reports of the antioxidative activity of other fungi induced by ICZ or amphotericin B (AmB) [34, 35], we found that the low concentration of these two antifungal agents had no effect on the superoxide dismutase (SOD) activity of phagocytized C. glabrata
Summary
Candida is generally regarded as a nonpathogenic symbiotic microbe of human mucosal tissue that occasionally causes opportunistic infections. Previous epidemiological studies from 2005 showed that the proportion of candidemia caused by Candida glabrata (C. glabrata) in public hospitals did not exceed 5–8% [1, 2]. With the increasing use of various iatrogenic catheters, immunosuppressive agents during organ transplantation and anticancer treatment, broad-spectrum antibiotics, and the increase in HIV infection, infections caused by Candida spp. have tended to be more invasive in deep organs and manifest as sepsis, fungemia, and other life-threatening conditions. Candidemia caused by C. glabrata accounts for 10.6% of fungemia [3]. According to the ARTEMIS Global Antifungal Monitoring Project, C. glabrata accounted for 10.2%– 11.7% of all Candida spp. strains isolated from June 1997 to December 2007 [5]. A multicenter prospective survey of severe invasive Candida infections in China showed that
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Schedule a callMore From: The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale
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