Cdc42 promotes host defenses against fatal infection
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Cdc42 promotes host defenses against fatal infection. / Lee, Keunwook; Boyd, Kelli L; Parekh, Diptiben V; Kehl-Fie, Thomas E; Baldwin, H Scott; Brakebusch, Cord; Skaar, Eric P; Boothby, Mark; Zent, Roy.
I: Infection and Immunity, Bind 81, Nr. 8, 20.05.2013, s. 2714-2723.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Cdc42 promotes host defenses against fatal infection
AU - Lee, Keunwook
AU - Boyd, Kelli L
AU - Parekh, Diptiben V
AU - Kehl-Fie, Thomas E
AU - Baldwin, H Scott
AU - Brakebusch, Cord
AU - Skaar, Eric P
AU - Boothby, Mark
AU - Zent, Roy
PY - 2013/5/20
Y1 - 2013/5/20
N2 - The small Rho GTPase, Cdc42, regulates key signaling pathways required for multiple cell functions including maintenance of shape, polarity, proliferation, invasion, migration, differentiation and morphogenesis. As the role of Cdc42-dependent signaling in fibroblasts in vivo is unknown, we attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections that were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also showed that in addition to fibroblasts, the FSP-1 cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this non-specific cre mouse we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate immunity.
AB - The small Rho GTPase, Cdc42, regulates key signaling pathways required for multiple cell functions including maintenance of shape, polarity, proliferation, invasion, migration, differentiation and morphogenesis. As the role of Cdc42-dependent signaling in fibroblasts in vivo is unknown, we attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections that were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also showed that in addition to fibroblasts, the FSP-1 cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this non-specific cre mouse we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate immunity.
U2 - 10.1128/IAI.01114-12
DO - 10.1128/IAI.01114-12
M3 - Journal article
C2 - 23690402
VL - 81
SP - 2714
EP - 2723
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 8
ER -
ID: 45826141