title: A Role for PML in Innate Immunity.
abstract: The promyelocytic leukemia gene (PML) of acute promyelocytic leukemia is an established tumor suppressor gene with critical functions in growth suppression, induction of apoptosis, and cellular senescence. Interestingly, although less studied, PML seems to play a key role also in immune response to viral infection. Herein, we report that Pml(-/-) mice spontaneously develop an atypical invasive and lethal granulomatous lesion known as botryomycosis (BTM). In Pml(-/-) mice, BTM is the result of impaired function of macrophages, whereby they fail to become activated and are thus unable to clear pathogenic microorganisms. Accordingly, Pml(-/-) mice are resistant to lipopolysaccharide (LPS)-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-κB prosurvival pathway. These results not only shed light on a new fundamental function of PML in innate immunity, but they also point to a proto-oncogenic role for PML in certain cellular and pathological contexts.
authors.affiliation: Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lunardi
authors.forename: Mirella
authors.initials: M
authors.lastname: Gaboli
authors.forename: Marco
authors.initials: M
authors.lastname: Giorgio
authors.forename: Roberta
authors.initials: R
authors.lastname: Rivi
authors.forename: Anne
authors.initials: A
authors.lastname: Bygrave
authors.forename: Michael
authors.initials: M
authors.lastname: Antoniou
authors.forename: Dubravka
authors.initials: D
authors.lastname: Drabek
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
authors.forename: Marta
authors.initials: M
authors.lastname: Fagioli
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salmena
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Lucio
authors.initials: L
authors.lastname: Luzzatto
authors.forename: Pier Giuseppe
authors.initials: PG
authors.lastname: Pelicci
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi