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 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.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Keunwook
authors.initials: K
authors.lastname: Lee
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Boyd
authors.forename: Diptiben V
authors.initials: DV
authors.lastname: Parekh
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Kehl-Fie
authors.forename: H Scott
authors.initials: HS
authors.lastname: Baldwin
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
authors.forename: Mark
authors.initials: M
authors.lastname: Boothby
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D007239:Infections / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000276:immunology*
chemical_list: D020764:cdc42 GTP-Binding Protein