interleukin-8 and Candidiasis--Invasive

Invasive candidiasis is a healthcare-associated fungal infection with a high mortality rate. Neutrophils, the first line of defense during fungal infections, express the immunoregulatory Candida albicans receptors CEACAM1, CEACAM3, and CEACAM6. We analyzed the effects of specific antibodies on C. albicans-induced neutrophil responses. CEACAM6 ligation by 1H7-4B and to some extent CEACAM1 ligation by B3-17, but not CEACAM3 ligation by 308/3-3, resulted in the immediate release of stored CXCL8 and altered transcriptional responses of the C. albicans-stimulated neutrophils. Integrated network analyses and dynamic simulations of signaling cascades predicted alterations in apoptosis and cytokine secretion. We verified that CEACAM6 ligation enhanced Candida-induced neutrophil apoptosis and increased long-term IL-1β/IL-6 release in responses to C. albicans. CEACAM3 ligation, but not CEACAM1 ligation, increased the long-term release of pro-inflammatory IL-1β/IL-6. Taken together, we demonstrated for the first time that ligation of CEACAM receptors differentially affects the regulation of C. albicans-induced immune functions in human neutrophils.

Topics: Antibodies, Monoclonal; Antigens, CD; Apoptosis; Candida albicans; Candidiasis, Invasive; Carcinoembryonic Antigen; Cell Adhesion Molecules; Cytokines; Female; GPI-Linked Proteins; Humans; Immunomodulation; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Neutrophils

The aim of this study was to investigate the role of cytokine genes in the susceptibility to Candida infection. A total of 275 consecutive patients diagnosed with Candida infection were selected between May 2010 and May 2011, along with 305 uninfected controls. Genotyping of the IL-1β gene polymorphisms (IL1β) rs1143634, IL1βrs16944, IL8 rs4073, IL10 rs1800872, and IL10 rs1800896 was carried out using a 384-well plate format on the Sequenom MassARRAY platform. Patients with invasive Candida infections were more likely to have had an immunocompromised state, hematopoietic stem cell transplantation, solid organ transplant, solid tumor, chemotherapy within the past three months, neutropenia, surgery within the past 30 days, acute renal failure, liver failure, and/or median baseline serum creatinine. Conditional logistic regression analyses found that individuals with the rs1800896 GG genotype were associated with a higher risk of invasive Candida infections than those carrying the AA genotype (odds ratio = 0.61, 95% confidence interval = 0.37-0.94). From the results of this case-control study, we suggest that the cytokine IL-10 gene rs1800896 polymorphism might play a role in the etiology of invasive Candida infections.

Topics: Acute Kidney Injury; Adult; Aged; Alleles; Candida; Candidiasis, Invasive; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Immunocompromised Host; Interleukin-10; Interleukin-1beta; Interleukin-8; Liver Failure; Logistic Models; Male; Middle Aged; Neoplasms; Polymorphism, Single Nucleotide