Modulation of neutrophil function in host defense against disseminated Candida albicans infection in mice.
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.
Kullberg
B J
BJ
Department of Medicine, Catholic University Nijmegen and University Hospital, Nijmegen, The Netherlands.
Netea
M G
MG
Vonk
A G
AG
van der Meer
J W
JW
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
D000935:Antifungal Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015725:Fluconazole