title: Modulation of neutrophil function in host defense against disseminated Candida albicans infection in mice.
abstract: Neutrophils (PMNs) constitute the main mechanism of host defense against acute invasive and disseminated candidiasis. Recent studies have demonstrated that tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) play an important role in the recruitment of PMNs at the site of invasive Candida infection. In the absence of either TNFalpha or IL-6, the course of experimental disseminated candidiasis is more severe, due to defective PMN recruitment. Treatment of mice with recombinant G-CSF (rG-CSF) leads to a significantly reduced mortality during disseminated candidiasis. The outgrowth of Candida albicans from the organs of rG-CSF-treated mice is significantly decreased. Treatment with the combination of rG-CSF and fluconazole has an additive effect on the reduction of fungal load in the organs. In subacute or chronic disseminated Candida infection, rG-CSF is less effective, indicating that neutrophil recruitment and activation are crucial in acute, life-threatening candidiasis, whereas other host defense mechanisms control the outcome of less overwhelming invasive Candida infection.
authors.affiliation: Department of Medicine, Catholic University Nijmegen and University Hospital, Nijmegen, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: A G
authors.initials: AG
authors.lastname: Vonk
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000188:drug therapy / Q000276:immunology*; D015725:Fluconazole / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D051379:Mice; D009504:Neutrophils / Q000276:immunology*; D011994:Recombinant Proteins
chemical_list: D000935:Antifungal Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015725:Fluconazole