A role for PML in innate immunity

Andrea Lunardi, Mirella Gaboli, Marco Giorgio, Roberta Rivi, Anne Bygrave, Michael Antoniou, Dubravka Drabek, Elaine Dzierzak, Marta Fagioli, Leonardo Salmena, Marina Botto, Carlos Cordon-Cardo, Lucio Luzzatto, Pier Giuseppe Pelicci, Frank Grosveld, Pier Paolo Pandolfi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)10-19
Number of pages10
JournalGenes and Cancer
Volume2
Issue number1
DOIs
Publication statusPublished - 2011

Keywords

  • Botryomycosis
  • Innate immunity
  • Pml

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'A role for PML in innate immunity'. Together they form a unique fingerprint.

  • Cite this

    Lunardi, A., Gaboli, M., Giorgio, M., Rivi, R., Bygrave, A., Antoniou, M., Drabek, D., Dzierzak, E., Fagioli, M., Salmena, L., Botto, M., Cordon-Cardo, C., Luzzatto, L., Pelicci, P. G., Grosveld, F., & Pandolfi, P. P. (2011). A role for PML in innate immunity. Genes and Cancer, 2(1), 10-19. https://doi.org/10.1177/1947601911402682