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: Article

35 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

Fingerprint

Mycobacterium Infections
Mycobacterium tuberculosis
Innate Immunity
Liposomes
Phosphatidic Acids
Phagocytes
Phagosomes
Interleukin-1
Tumor Necrosis Factor-alpha
Interleukin-27
Macrophages
Interleukin-23
Interleukin-18
Phosphatidylserines
Isoniazid
Transforming Growth Factors
Bronchoalveolar Lavage
Interleukin-12
Pulmonary Tuberculosis
Interleukin-10

All Science Journal Classification (ASJC) codes

  • General

Cita questo

Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection. / Dieli, Francesco; Caccamo, Nadia Rosalia; Di Liberto, Diana; Savage, Nigel D.; Delogu, Giovanni; Papi, Massimiliano; Quintiliani, Gianluca; Greco, Emanuela; Ciccaglione, Anna Rita; Marcantonio, Cinzia; Fraziano, Maurizio; Alma, Mario; Sarmati, Loredana; Serafino, Annalucia; Nisini, Roberto; Goletti, Delia; Altieri, Alfonso; Ottenhoff, Tom H.; Andreoni, Massimo; Martino, Angelo; Santucci, Marilina B.; De Spirito, Marco; Maulucci, Giuseppe.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, 2012, pag. 1360-1368.

Risultato della ricerca: Article

Dieli, F, Caccamo, NR, Di Liberto, D, Savage, ND, Delogu, G, Papi, M, Quintiliani, G, Greco, E, Ciccaglione, AR, Marcantonio, C, Fraziano, M, Alma, M, Sarmati, L, Serafino, A, Nisini, R, Goletti, D, Altieri, A, Ottenhoff, TH, Andreoni, M, Martino, A, Santucci, MB, De Spirito, M & Maulucci, G 2012, 'Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection', Proceedings of the National Academy of Sciences of the United States of America, vol. 109, pagg. 1360-1368.
Dieli, Francesco ; Caccamo, Nadia Rosalia ; Di Liberto, Diana ; Savage, Nigel D. ; Delogu, Giovanni ; Papi, Massimiliano ; Quintiliani, Gianluca ; Greco, Emanuela ; Ciccaglione, Anna Rita ; Marcantonio, Cinzia ; Fraziano, Maurizio ; Alma, Mario ; Sarmati, Loredana ; Serafino, Annalucia ; Nisini, Roberto ; Goletti, Delia ; Altieri, Alfonso ; Ottenhoff, Tom H. ; Andreoni, Massimo ; Martino, Angelo ; Santucci, Marilina B. ; De Spirito, Marco ; Maulucci, Giuseppe. / Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109. pagg. 1360-1368.
@article{c7e7b7124ae24ac9825e92fc7837bf97,
title = "Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection",
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.",
author = "Francesco Dieli and Caccamo, {Nadia Rosalia} and {Di Liberto}, Diana and Savage, {Nigel D.} and Giovanni Delogu and Massimiliano Papi and Gianluca Quintiliani and Emanuela Greco and Ciccaglione, {Anna Rita} and Cinzia Marcantonio and Maurizio Fraziano and Mario Alma and Loredana Sarmati and Annalucia Serafino and Roberto Nisini and Delia Goletti and Alfonso Altieri and Ottenhoff, {Tom H.} and Massimo Andreoni and Angelo Martino and Santucci, {Marilina B.} and {De Spirito}, Marco and Giuseppe Maulucci",
year = "2012",
language = "English",
volume = "109",
pages = "1360--1368",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",

}

TY - JOUR

T1 - Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection

AU - Dieli, Francesco

AU - Caccamo, Nadia Rosalia

AU - Di Liberto, Diana

AU - Savage, Nigel D.

AU - Delogu, Giovanni

AU - Papi, Massimiliano

AU - Quintiliani, Gianluca

AU - Greco, Emanuela

AU - Ciccaglione, Anna Rita

AU - Marcantonio, Cinzia

AU - Fraziano, Maurizio

AU - Alma, Mario

AU - Sarmati, Loredana

AU - Serafino, Annalucia

AU - Nisini, Roberto

AU - Goletti, Delia

AU - Altieri, Alfonso

AU - Ottenhoff, Tom H.

AU - Andreoni, Massimo

AU - Martino, Angelo

AU - Santucci, Marilina B.

AU - De Spirito, Marco

AU - Maulucci, Giuseppe

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10447/73214

M3 - Article

VL - 109

SP - 1360

EP - 1368

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

ER -