Mice lacking both G-CSF and IL-6 are more susceptible to Candida albicans infection: critical role of neutrophils in defense against Candida albicans.
Neutrophils play an important role in the host's defense against infection with various pathogenic organisms. Granulocyte colony stimulating factor (G-CSF) is regarded as a major regulator of neutrophil production and function. Mice lacking G-CSF or its receptor are neutropenic. IL-6 is another cytokine that has been shown to promote neutrophil production and modulate the function of many types of immune cells. We have analyzed G-CSF/IL-6 double deficient (G-CSF(- / - )/IL-6(- / - )) mice to gain an insight into the possible contribution of IL-6 to the residual granulopoiesis in G-CSF-deficient (G-CSF(- / - )) mice. Furthermore, we have evaluated the ability of G-CSF(- / - )/IL-6(- / - ) mice to combat an experimental infection with Candida albicans. Our data shows that IL-6 plays a role in granulopoiesis during early post natal period but it is dispensable for steady-state granulopoiesis in adult mice. However, adult G-CSF(- / - )/IL-6(- / - ) mice are more susceptible to Candida infection than similarly infected G-CSF(- / - ) mice. Although, the candidacidal function of neutrophils of G-CSF(- / - )/IL-6(- / - ) mice is deficient, the ability to produce IFN-gamma and TNF-alpha in response to Candida infection is not compromised. Similarly, nitric oxide production by peritoneal macrophages from G-CSF(- / - )/IL-6(- / - ) mice in response to Candida is comparable to G-CSF(- / - ) mice.
Basu
Sunanda
S
Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch, Royal Melbourne Hospital, Melbourne, Vic., Australia. sunbasu@iupui.edu
Quilici
Cathy
C
Zhang
Hui-Hua
HH
Grail
Dianne
D
Dunn
Ashley R
AR
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002176:Candida albicans / Q000378:metabolism*; D002177:Candidiasis / Q000378:metabolism* / Q000382:microbiology; D002470:Cell Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma