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

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Cdc42 Promotes Host Defenses against Fatal Infection

Journal article

Open access

Peer reviewed

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 and Roy Zent

Infection and immunity, Vol.81(8), pp.2714-2723

08/01/2013

DOI: 10.1128/IAI.01114-12

PMCID: PMC3719566

PMID: 23690402

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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 Cdc42 fl/fl mouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;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 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.

Host Response and Inflammation

Details

Title: Subtitle: Cdc42 Promotes Host Defenses against Fatal Infection
Creators: Keunwook Lee - Vanderbilt University
Kelli L. Boyd - Vanderbilt University
Diptiben V. Parekh - Vanderbilt University
Thomas E. Kehl-Fie - Vanderbilt University
H. Scott Baldwin - Vanderbilt University
Cord Brakebusch - University of Copenhagen
Eric P. Skaar - Vanderbilt University
Mark Boothby - Vanderbilt University
Roy Zent - Vanderbilt University
Resource Type: Journal article
Publication Details: Infection and immunity, Vol.81(8), pp.2714-2723
Publisher: American Society for Microbiology
DOI: 10.1128/IAI.01114-12
PMID: 23690402
PMCID: PMC3719566
ISSN: 0019-9567
eISSN: 1098-5522
Language: English
Date published: 08/01/2013
Academic Unit: Microbiology and Immunology
Record Identifier: 9984618642902771

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