Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection

Francesco Dieli, Nadia Rosalia Caccamo, Diana Di Liberto, Nigel D. Savage, Giovanni Delogu, Massimiliano Papi, Gianluca Quintiliani, Emanuela Greco, Anna Rita Ciccaglione, Cinzia Marcantonio, Maurizio Fraziano, Mario Alma, Loredana Sarmati, Annalucia Serafino, Roberto Nisini, Delia Goletti, Alfonso Altieri, Tom H. Ottenhoff, Massimo Andreoni, Angelo MartinoMarilina B. Santucci, Marco De Spirito, Giuseppe Maulucci

Risultato della ricerca: Articlepeer review

38 Citazioni (Scopus)

Abstract

We have generated unique asymmetric liposomes with phosphatidylserine (PS) distributed at the outer membrane surface to resemble apoptotic bodies and phosphatidic acid (PA) at the inner layer as a strategy to enhance innate antimycobacterial activity in phagocytes while limiting the inflammatory response. Results show that these apoptotic body-like liposomes carrying PA (ABL/PA) (i) are more efficiently internalized by human macrophages than by nonprofessional phagocytes, (ii) induce cytosolic Ca(2+) influx, (iii) promote Ca(2+)-dependent maturation of phagolysosomes containing Mycobacterium tuberculosis (MTB), (iv) induce Ca(2+)-dependent reactive oxygen species (ROS) production, (v) inhibit intracellular mycobacterial growth in differentiated THP-1 cells as well as in type-1 and -2 human macrophages, and (vi) down-regulate tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, IL-18, and IL-23 and up-regulate transforming growth factor (TGF)-β without altering IL-10, IL-27, and IL-6 mRNA expression. Also, ABL/PA promoted intracellular killing of M. tuberculosis in bronchoalveolar lavage cells from patients with active pulmonary tuberculosis. Furthermore, the treatment of MTB-infected mice with ABL/PA, in combination or not with isoniazid (INH), dramatically reduced lung and, to a lesser extent, liver and spleen mycobacterial loads, with a concomitant 10-fold reduction of serum TNF-α, IL-1β, and IFN-γ compared with that in untreated mice. Altogether, these results suggest that apoptotic body-like liposomes may be used as a Janus-faced immunotherapeutic platform to deliver polar secondary lipid messengers, such as PA, into phagocytes to improve and recover phagolysosome biogenesis and pathogen killing while limiting the inflammatory response.
Lingua originaleEnglish
pagine (da-a)1360-1368
Numero di pagine9
RivistaProceedings of the National Academy of Sciences of the United States of America
Volume109
Stato di pubblicazionePublished - 2012

All Science Journal Classification (ASJC) codes

  • General

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