Janus-faced liposomes enhance antimicrobial innate immune response in
            <i>Mycobacterium tuberculosis</i>
            infection

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

doi:10.1073/pnas.1200484109

Cited by 54 publications

(66 citation statements)

References 59 publications

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“…The prolonged and complex anti-TB chemotherapy for MDR-and XDR-TB cases includes antibiotics that are very expensive. For instance, combining direct and indirect costs, the average cost per-TB case in the original EU states was estimated at 10.282 EUR for drug susceptible TB, 57,213 EUR for MDR-TB and 170,744 EUR for XDR-TB, with a total cost for TB treatment in Europe surpassing the 0.5 billion EUR in 2011 [3]. Hence, the emergence of drug resistance is posing a major threat to control TB, with important health, social and economic consequences [2].…”

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confidence: 99%

Host Directed Therapies for Tuberculosis: Futures Strategies for an Ancient Disease

Palucci

Delogu

2018

Chemotherapy

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The emergence and spread of drug-resistant strains of Mycobacterium tuberculosis is worsening the global threat of tuberculosis (TB). There is a need and urgency for the development of new treatments for TB, for the management of drug resistant TB (MDR-TB) and for improved regimens against drug-susceptible TB, with the goal of reducing toxicity and length of therapy that will boost patience compliance. The paucity of new drugs is a major obstacle to design new regimens while host-directed therapies (HDTs) are emerging as a promising area of research and are opening new avenues to fight TB. In this review, we discuss examples of potentially promising strategies aimed at improving the host response to M. tuberculosis, and argue how a better understanding of TB pathogenesis, with the fine characterization of the immunological mediators involved, may pave the way for the design of new therapies, the identification of new drugs or the repurposing of some already in use for other diseases. We emphasize that any HDTs shall be included as adjunct therapy to the drug-combination regimens already in use for TB, with the goal to reduce tissue damage and immunopathology and enhance bacterial clearance. We anticipate that the benefits of HDTs against TB will be highest against MDR-TB, where the activity of current regimens is poor and the cost high.

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Host Directed Therapies for Tuberculosis: Futures Strategies for an Ancient Disease

Palucci

Delogu

2018

Chemotherapy

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“…If the diagnosis and treatment of bone tuberculosis is not timely, it can cause spinal deformity, limited activity, and even paraplegia, seriously affecting the quality of life of the patients. Mycobacterium tuberculosis invades the body and multiplies in cells and causes an inflammatory response and therefore, disrupts the function of the immune system [29]. The immune mechanism of the host cells, thus plays an important role in the growth of Mycobacterium tuberculosis.…”

Section: Discussionmentioning

confidence: 99%

Anti-IFN-γ Antibody Promotes Osteoclastogenesis in Human Bone Marrow Monocyte-Derived Macrophages Co-Cultured with Tuberculosis-Activated Th1 Cells

Deng¹,

Sun²,

Luo³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Tuberculosis induces bone loss and activates Th1 cells that play an important role in the host defense of Bacille Calmette-Guérin tuberculosis vaccine. However, the role of tuberculosis-activated Th1 cells in differentiation of osteoclast precursors to osteoclasts is unclear. As secretion of IFN-γ in Th1 cells is induced by tuberculosis, we aimed to investigate the role of anti-IFN-γ antibody on the differentiation and activation of osteoclasts in bone marrow monocyte-derived macrophages (BMMs). Methods: BMMs were isolated and co-cultured with CD4+T helper 1 cells (Th1 cells), pretreated with anti-IFN-γ antibody. Then, cell proliferation, expression and release of cytokines, formation of actin ring, differentiation of osteoclasts and bone resorption function were measured by CCK8 assay, qRT-PCR/Western blot/flow cytometry, ELISA, immunofluorescence, tartrate-resistant acidic phosphatase (TRAP) staining and bone absorbance assay, respectively. Results: Anti-IFN-γ antibody inhibited the cell viability of BMMs, and induced the expressions of RANKL, TNF-α, NF-κB and TRAF6 in BMMs. In addition, it led to increased expression levels of RANK on cell surfaces, and increased production of RANKL, TNF-α, MCP-1 and SDF-1. Anti-IFN-γ antibody also induced the expression of osteoclast differentiation factor and actin ring formation, but inhibited the expression of osteoprotegerin. TRAP staining and bone resorption assays showed that anti-IFN-γ antibody induced an increase in osteoclast formation and bone resorption. Conclusion: The anti-IFN-γ antibody induced osteoclast formation, and is probably mediated by RANKL-induced activation of NF-κB, that induces TRAF6 in the RANKL-RANK signaling pathway. Our data suggest an inhibitory role for IFN-γ in osteoclast formation induced by tuberculosis.

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“…In vivo studies utilizing these phosphatidic acid-loaded liposomes in TB-infected mice demonstrated their ability to induce heightened immunological responses, increase reactive oxygen species levels within phagolysosomes and facilitate intracellular mycobacterial killing within macrophages. [33] …”

Section: Liposomes As Drug Delivery Systemsmentioning

confidence: 99%

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections

Liang

Ding

et al. 2017

Adv Healthcare Materials

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worldwide was estimated at a staggering 10.4 million, with a significant percentage (10%) resulting from concomitant HIV-TB coinfections. [1] Given the closely knitted association between TB infections and poor sanitation/poverty, it thus comes with no surprise that an overwhelming majority of disease burden (60%) is actually shouldered by countries from the developing world (Figure 1). [1] TB infections are compounded by the emergence of multidrug resistance (MDR). In spite of the tremendous amount of resources and research dollars that have been devoted to TB research, TB diagnostics and treatment outcomes still remain startlingly poor. TB remains worryingly underreported, under-diagnosed and undertreated. A 4.3 million gap was reported between incident and notified TB cases, chiefly in developing countries; majority of TB infections remain latent and unreported, and only 30% of new incident TB cases were subjected to drug susceptibility testing. [1] The Xpert Mycobacterium Tuberculosis (MTB)/RIF assay remains the only available WHOrecommended rapid diagnostic platform for detection of TB and drug (rifampicin) resistance. Treatment success rates are highly variable, ranging from 28% (extensively drug-resistant strains) to 83% (garden strains) of TB. The rate of decline in TB incidence has remained stagnant at 1.5% annually over the past decade, far lagging behind the 5% projected by the WHO's End TB Strategy. Against such a backdrop, TB remains firmly entrenched among the top 10 causes of death worldwide. [2] To this end, the WHO has since 2015, adopted the End TB Strategy in an effort to stem this burgeoning epidemic. Major diagnostic and treatment gaps in TB management still remain, and these need to be addressed to effectively curtail TB spread and its impact on global health. Pathogenesis of TB InfectionsMTB is the infectious agent responsible for TB infections. It originates from the family Mycobacteriaceae and is an obligate bacteria chiefly spread via air droplets.

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

Cited by 54 publications

References 59 publications

Host Directed Therapies for Tuberculosis: Futures Strategies for an Ancient Disease

Host Directed Therapies for Tuberculosis: Futures Strategies for an Ancient Disease

Anti-IFN-γ Antibody Promotes Osteoclastogenesis in Human Bone Marrow Monocyte-Derived Macrophages Co-Cultured with Tuberculosis-Activated Th1 Cells

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections

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