Cdc42 promotes host defenses against fatal infection

Keunwook Lee; Kelli L Boyd; Diptiben V Parekh; Thomas E Kehl-Fie; H Scott Baldwin; Cord Brakebusch; Eric P Skaar; Mark Boothby; Roy Zent

doi:10.1128/IAI.01114-12

Cdc42 promotes host defenses against fatal infection

Keunwook Lee, Kelli L Boyd, Diptiben V Parekh, Thomas E Kehl-Fie, H Scott Baldwin, Cord Brakebusch, Eric P Skaar, Mark Boothby, Roy Zent

9 Citations (Scopus)

Abstract

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 Cdc42fl/flmouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;Cdc42fl/flmice 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 show that in addition to fibroblasts, FSP1-Cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this nonspecific 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.

Original language	English
Journal	Infection and Immunity
Volume	81
Issue number	8
Pages (from-to)	2714-2723
Number of pages	10
ISSN	0019-9567
DOIs	https://doi.org/10.1128/IAI.01114-12
Publication status	Published - Aug 2013

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title = "Cdc42 promotes host defenses against fatal infection",

abstract = "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 Cdc42fl/flmouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;Cdc42fl/flmice 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 show that in addition to fibroblasts, FSP1-Cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this nonspecific 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.",

author = "Keunwook Lee and Boyd, {Kelli L} and Parekh, {Diptiben V} and Kehl-Fie, {Thomas E} and Baldwin, {H Scott} and Cord Brakebusch and Skaar, {Eric P} and Mark Boothby and Roy Zent",

year = "2013",

month = aug,

doi = "10.1128/IAI.01114-12",

language = "English",

volume = "81",

pages = "2714--2723",

journal = "Infection and Immunity",

issn = "0019-9567",

publisher = "American Society for Microbiology",

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TY - JOUR

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 - 2013/8

Y1 - 2013/8

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 Cdc42fl/flmouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;Cdc42fl/flmice 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 show that in addition to fibroblasts, FSP1-Cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this nonspecific 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 Cdc42fl/flmouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;Cdc42fl/flmice 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 show that in addition to fibroblasts, FSP1-Cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this nonspecific 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

SN - 0019-9567

VL - 81

SP - 2714

EP - 2723

JO - Infection and Immunity

JF - Infection and Immunity

IS - 8

ER -

Cdc42 promotes host defenses against fatal infection

Abstract

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