Abstract:
:Mycolic acid (MA), a major lipid component of Mycobacterium tuberculosis (Mtb) cell wall, can be presented by the non-polymorphic antigen presenting molecule CD1b to T cells isolated from Mtb-infected individuals. These MA-specific CD1b-restricted T cells are cytotoxic, produce Th1 cytokines, and form memory populations, suggesting that MA can be explored as a potential subunit vaccine candidate for TB. However, the controlled elicitation of MA-specific T cell responses has been challenging due to difficulties in the targeted delivery of lipid antigens and a lack of suitable animal models. In this study, we generated MA-loaded micellar nanocarriers (MA-Mc) comprised of self-assembled poly(ethylene glycol)-bl-poly(propylene sulfide; PEG-PPS) copolymers conjugated to an acid sensitive fluorophore to enhance intracellular delivery of MA to phagocytic immune cells. Using humanized CD1 transgenic (hCD1Tg) mice, we found these nanobiomaterials to be endocytosed by bone marrow-derived dendritic cells (DCs) and localized to lysosomal compartments. Additionally, MA-Mc demonstrated superior efficacy over free MA in activating MA-specific TCR transgenic (DN1) T cells in vitro. Following intranasal immunization, MA-Mc were primarily taken up by alveolar macrophages and DCs in the lung and induced activation and proliferation of adoptively transferred DN1 T cells. Furthermore, intranasal immunization with MA-Mc induced MA-specific T cell responses in the lungs of hCD1Tg mice. Collectively, our data demonstrates that pulmonary delivery of MA via PEG-PPS micelles to DCs can elicit potent CD1b-restricted T cell responses both in vitro and in vivo and MA-Mc could be explored as subunit vaccines against Mtb infection.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Shang S,Kats D,Cao L,Morgun E,Velluto D,He Y,Xu Q,Wang CR,Scott EAdoi
10.3389/fimmu.2018.02709subject
Has Abstractpub_date
2018-11-27 00:00:00pages
2709issn
1664-3224journal_volume
9pub_type
杂志文章abstract::Several approaches have been developed to improve or replace the only available vaccine for tuberculosis (TB), BCG (Bacille Calmette Guerin). The development of subunit protein vaccines is a promising strategy because it combines specificity and safety. In addition, subunit protein vaccines can be designed to have sel...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00188
更新日期:2014-04-23 00:00:00
abstract::Therapy with Tyrosine Kinase Inhibitors (TKI) aiming stable deep molecular response is the gold standard to treat Chronic Myeloid Leukemia (CML). NKT-like cells (CD3+CD56+) combine characteristics of T and NK cells. The physiopathological role of these cells remains unknown although the literature refers their associa...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02493
更新日期:2019-10-22 00:00:00
abstract::Monocytes in humans consist of 3 subsets; CD14+CD16- (classical), CD14+CD16+ (intermediate) and CD14dimCD16+ (non-classical), which exhibit distinct and heterogeneous responses to activation. During acute inflammation CD14+CD16- monocytes are significantly elevated and migrate to the sites of injury via the adhesion c...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02054
更新日期:2019-09-06 00:00:00
abstract::The onset of hepatic disorders in patients with systemic lupus erythematosus (SLE) is frequent; however, the etiology and liver pathogenesis of SLE remain unknown. In the present study, the role of hepatic deposited immunoglobulin G (IgG) in SLE-derived liver damage was investigated. From a retrospective analysis of t...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01457
更新日期:2018-06-25 00:00:00
abstract::Intravenous IgG (IVIg) contains polyclonal immunoglobulin G (IgG) from thousands of donors. It is administered at a low dose at regular intervals as antibody replacement therapy and at a higher dose as immunomodulatory treatment in various auto-immune or auto-inflammatory diseases. The working mechanism of immunomodul...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00674
更新日期:2015-01-21 00:00:00
abstract:Background:Chagas disease caused by Trypanosoma cruzi (T. cruzi) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between IL1B, IL6, IL17A, or IL18 polymorphism p...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.521409
更新日期:2020-10-22 00:00:00
abstract::A common feature of many acute and chronic oral diseases is microbial-induced inflammation. Innate immune responses are the first line of defense against pathogenic microorganisms and are initiated by pattern recognition receptors (PRRs) that specifically recognize pathogen-associated molecular patterns and danger-ass...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01487
更新日期:2020-08-13 00:00:00
abstract::Background: Critically ill patients, especially following trauma or extensive surgery, experience a systemic immune response, consisting of a pro-inflammatory as well as a counterbalancing anti-inflammatory response. Pro-inflammation is necessary for the initiation of homeostatic control and wound healing of the organ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00432
更新日期:2019-03-12 00:00:00
abstract::Volcanic ash is a heterogeneous mineral dust that is typically composed of a mixture of amorphous (glass) and crystalline (mineral) fragments. It commonly contains an abundance of the crystalline silica (SiO2) polymorph cristobalite. Inhalation of crystalline silica can induce inflammation by stimulating the NLRP3 inf...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.02000
更新日期:2018-01-22 00:00:00
abstract::Dendritic epidermal T cells (DETCs) and dermal Vγ4 T cells engage in wound re-epithelialization and skin inflammation. However, it remains unknown whether a functional link between Vγ4 T cell pro-inflammation and DETC pro-healing exists to affect the outcome of skin wound closure. Here, we revealed that Vγ4 T cell-der...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00240
更新日期:2018-02-12 00:00:00
abstract::TLR8 is the major endosomal sensor of degraded RNA in human monocytes and macrophages. It has been implicated in the sensing of viruses and more recently also bacteria. We previously identified a TLR8-IFN regulatory factor 5 (IRF5) signaling pathway that mediates IFNβ and interleukin-12 (IL-12) induction by Staphyloco...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01243
更新日期:2017-10-03 00:00:00
abstract::Autophagy comprises a heterogeneous group of cellular pathways that enables eukaryotic cells to deliver cytoplasmic constituents for lysosomal degradation, to recycle nutrients, and to survive during starvation. In addition to these primordial functions, autophagy has emerged as a key mechanism in orchestrating innate...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00165
更新日期:2017-02-27 00:00:00
abstract::Interleukin 10 is a central regulator of the antigen-presenting function of myeloid cells. It exerts immunomodulatory effects in vivo and induces a regulatory phenotype in monocyte-derived cells in vitro. We analyzed phenotype and function of monocytic cells in vitro in relation to the cytokine milieu and the timing o...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01484
更新日期:2019-06-28 00:00:00
abstract::Background: Chagas cardiomyopathy is the main fibrosing myocarditis among known heart diseases. Development of cardiomyopathy has been related to extracellular matrix (ECM) remodeling, which are controlled by matrix metalloproteinases (MMPs) and cytokines, especially interleukin (IL)-1β. The convertion of 31KDa inacti...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00800
更新日期:2019-04-18 00:00:00
abstract::[This corrects the article DOI: 10.3389/fimmu.2019.00917.]. ...
journal_title:Frontiers in immunology
pub_type: 已发布勘误
doi:10.3389/fimmu.2019.01528
更新日期:2019-07-02 00:00:00
abstract::Aquaculture production of crustaceans (mainly shrimp and crabs) has expanded globally, but disease outbreaks and pathogenic infections have hampered production in the last two decades. As invertebrates, crustaceans lack an adaptive immune system and mainly defend and protect themselves using their innate immune system...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.574721
更新日期:2020-11-05 00:00:00
abstract::Alloimmunity driving rejection in the context of solid organ transplantation can be grossly divided into mechanisms predominantly driven by either T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), though the co-existence of both types of rejections can be seen in a variable number of sampled gra...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00432
更新日期:2016-10-21 00:00:00
abstract::Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on central nervous system (CNS) myelin. Although CD4(+) T cell function in MS pathology has been extensively studied, there is also strong evidence that CD8(+) T lymphocytes play a key role. Intriguingly, CD8(+) T cells accumula...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00541
更新日期:2015-10-22 00:00:00
abstract::Dendritic cells (DCs) are antigen-presenting cells essential for the induction of adaptive immune responses. Their unprecedented ability to present antigens to T cells has made them excellent targets for vaccine development. In the last years, a new technology based on antigen delivery directly to different DC subsets...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01727
更新日期:2017-12-04 00:00:00
abstract::The so-called shock and kill therapies aim to combine HIV-1 reactivation by latency-reversing agents (LRA) with immune clearance to purge the HIV-1 reservoir. The clinical use of LRA has demonstrated detectable perturbations in the HIV-1 reservoir without measurable reductions to date. Consequently, fundamental questi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.03162
更新日期:2019-01-22 00:00:00
abstract::Food allergy is an atopic disease that is caused by the immune system targeting harmless food antigens that can result in life-threatening anaphylaxis. As humans and microbes have co-evolved, inevitably commensal microbes have a tremendous impact on our health. As such, the gut with its enormous microbial richness ref...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01853
更新日期:2020-08-14 00:00:00
abstract::The initiation of T-cell signaling is critically dependent on the function of the member of Src family tyrosine kinases, Lck. Upon T-cell antigen receptor (TCR) triggering, Lck kinase activity induces the nucleation of signal-transducing hubs that regulate the formation of complex signaling network and cytoskeletal re...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00449
更新日期:2016-10-27 00:00:00
abstract::CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells are essential to the balance between pro- and anti-inflammatory responses. There are two major subsets of Treg cells, "natural" Treg (nTreg) cells that develop in the thymus, and "induced" Treg (iTreg) cells that arise in the periphery from CD4(+) Foxp3(-) conventional...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00152
更新日期:2013-06-19 00:00:00
abstract::Sepsis is life-threatening organ dysfunction due to dysregulated response to infection. Patients with sepsis exhibit wide heterogeneity stemming from genetic, molecular, and clinical factors as well as differences in pathogens, creating challenges for the development of effective treatments. Several gaps in knowledge ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01502
更新日期:2018-06-28 00:00:00
abstract::Intravesical instillation of bacillus Calmette-Guérin (BCG) is used to treat superficial bladder cancer, either papillary tumors (after transurethral resection) or high-grade flat carcinomas (carcinoma in situ), reducing recurrence in about 70% of patients. Initially, BCG was proposed to work through an inflammatory r...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2015.00284
更新日期:2015-06-08 00:00:00
abstract::CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T cells that express an invariant T cell receptor (TCR) α-chain and recognize self and foreign glycolipid antigens. They can rapidly respond to agonist activation and stimulate an extensive array of immune responses. Thymic development and functio...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02653
更新日期:2018-11-14 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease including the cardiovascular system. Atherosclerosis is the most common cardiovascular complication of SLE and a significant risk factor for morbidity and mortality. Vascular damage/protection mechanism in SLE patients is out of balance, caused by...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.581385
更新日期:2020-11-11 00:00:00
abstract::Clematichinenoside AR (C-AR) is a triterpene saponin isolated from the root of Clematis manshurica Rupr., which is a herbal medicine used in traditional Chinese medicine for the treatment of arthritis. C-AR exerts anti-inflammatory and immunosuppressive properties, but little is known about its action in the suppressi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00532
更新日期:2016-12-07 00:00:00
abstract:BACKGROUND:Subjects are considered infected with Trypanosoma cruzi when tested positive by at least two out of three serological tests, whereas a positive result in only one of up to three tests is termed "serodiscordant" (SD). Assessment of parasite-specific T-cell responses may help discriminate the uninfected from i...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01141
更新日期:2017-09-15 00:00:00
abstract::Drugs formulated from monoclonal antibodies (mAbs) are clinically effective in various diseases. Repeated administration of mAbs, however, elicits an immune response in the form of anti-drug-antibodies (ADA), thereby reducing the drug's efficacy. Notwithstanding their importance, the molecular landscape of ADA and the...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02921
更新日期:2019-12-18 00:00:00