TY - JOUR
T1 - A Role for PML in Innate Immunity
AU - Lunardi, Andrea
AU - Gaboli, Mirella
AU - Giorgio, Marco
AU - Rivi, Roberta
AU - Bygrave, Anne
AU - Antoniou, Michael
AU - Drabek, Dubravka
AU - Dzierzak, Elaine
AU - Fagioli, Marta
AU - Salmena, Leonardo
AU - Botto, Marina
AU - Cordon-Cardo, Carlos
AU - Luzzatto, Lucio
AU - Pelicci, Pier Giuseppe
AU - Grosveld, Frank
AU - Pandolfi, Pier Paolo
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
U2 - 10.1177/1947601911402682
DO - 10.1177/1947601911402682
M3 - Article
C2 - 21779477
SN - 1947-6027
VL - 2
SP - 10
EP - 19
JO - Genes and Cancer
JF - Genes and Cancer
IS - 1
ER -