Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection
| العنوان: | Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection |
|---|---|
| المؤلفون: | Marco De Spirito, M. Santucci, Maurizio Fraziano, Roberto Nisini, Giuseppe Maulucci, Massimo Andreoni, Anna Rita Ciccaglione, Francesco Dieli, Tom H. M. Ottenhoff, Nadia Caccamo, Cinzia Marcantonio, Loredana Sarmati, Mario Giuseppe Alma, Delia Goletti, Diana Di Liberto, Massimiliano Papi, Giovanni Delogu, Alfonso Altieri, Annalucia Serafino, Emanuela Greco, Gianluca Quintiliani, Angelo Martino, Nigel D. L. Savage |
| المساهمون: | Greco, E, Quintiliani, G, Santucci, MB, Serafino, A, Ciccaglione, AR, Marcantonio, C, Papi, M, Maulucci, G, Delogu, G, Martino, A, Goletti, D, Sarmati, L, Andreoni, M, Altieri, A, Alma, M, Caccamo, N, Di Liberto, D, De Spirito, M, Savage, ND, Nisini, R, Dieli, F, Ottenhoff, TH, Fraziano, M |
| المصدر: | Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences, 109(21), E1360-E1368 Proceedings of the National Academy of Sciences; Vol 109 |
| بيانات النشر: | National Academy of Sciences, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Antitubercular Agents, Apoptosis, Settore MED/07, Mice, 0302 clinical medicine, Innate, Inbred BALB C, Mycobacterium tuberculosis, liposomes, 0303 health sciences, Mice, Inbred BALB C, Multidisciplinary, Leukemia, Tumor, biology, Macrophages, Leukemia, Monocytic, Acute, Animals, Calcium, Humans, Disease Models, Animal, Cell Line, Tumor, Immunity, Innate, Reactive Oxygen Species, Liposomes, Phosphatidylserines, Tuberculosis, Pulmonary, Adult, Bronchoalveolar Lavage Fluid, Middle Aged, Phagocytosis, Mycobacterium tuberculosis, Isoniazid, Interleukin, Pulmonary, Settore BIO/19, 3. Good health, PNAS Plus, Tumor necrosis factor alpha, Intracellular, Acute, Phagolysosome, Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA, Microbiology, Cell Line, 03 medical and health sciences, Tuberculosis, 030304 developmental biology, Settore MED/04 - Patologia Generale, therapy, Innate immune system, Monocytic, Animal, Immunity, biology.organism_classification, Immunology, Disease Models, 030215 immunology |
| الوصف: | 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. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c85ddfebc4768b0c66f6abcdae9ec190Test http://hdl.handle.net/10447/73214Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c85ddfebc4768b0c66f6abcdae9ec190 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |