Programmable Hamiltonian engineering with quadratic quantum Fourier transform

Quantum Fourier transform (QFT) is a widely used building block for quantum algorithms, whose scalable implementation is challenging in experiments. Here, we propose a protocol of quadratic quantum Fourier transform (QQFT), considering cold atoms confined in an optical lattice. This QQFT is equivalent to QFT in the single-particle subspace, and produces a different unitary operation in the entire Hilbert space. We show this QQFT protocol can be implemented using programmable laser potential with the digital-micromirror-device techniques recently developed in the experiments. The QQFT protocol enables programmable Hamiltonian engineering, and allows quantum simulations of Hamiltonian models, which are difficult to realize with conventional approaches. The flexibility of our approach is demonstrated by performing quantum simulations of one-dimensional Poincar\'{e} crystal physics and two-dimensional topological flat bands, where the QQFT protocol effectively generates the required long-range tunnelings despite the locality of the cold atom system. We find the discrete Poincar\'{e} symmetry and topological properties in the two examples respectively have robustness against a certain degree of noise that is potentially existent in the experimental realization. We expect this approach would open up wide opportunities for optical lattice based programmable quantum simulations.Comment: 10 pages, 5 figure

Mucosal CD8 T Cell Responses Are Shaped by Batf3-DC After Foodborne Listeria monocytogenes Infection

While immune responses have been rigorously examined after intravenous Listeria monocytogenes (Lm) infection, less is understood about its dissemination from the intestines or the induction of adaptive immunity after more physiologic models of foodborne infection. Consequently, this study focused on early events in the intestinal mucosa and draining mesenteric lymph nodes (MLN) using foodborne infection of mice with Lm modified to invade murine intestinal epithelium (InlAM Lm). InlAM Lm trafficked intracellularly from the intestines to the MLN and were associated with Batf3-independent dendritic cells (DC) in the lymphatics. Consistent with this, InlAM Lm initially disseminated from the gut to the MLN normally in Batf3–/– mice. Activated migratory DC accumulated in the MLN by 3 days post-infection and surrounded foci of InlAM Lm. At this time Batf3–/– mice displayed reduced InlAM Lm burdens, implicating cDC1 in maximal bacterial accumulation in the MLN. Batf3–/– mice also exhibited profound defects in the induction and gut-homing of InlAM Lm-specific effector CD8 T cells. Restoration of pathogen burden did not rescue antigen-specific CD8 T cell responses in Batf3–/– mice, indicating a critical role for Batf3 in generating anti-InlAM Lm immunity following foodborne infection. Collectively, these data suggest that DC play diverse, dynamic roles in the early events following foodborne InlAM Lm infection and in driving the establishment of intestinal Lm-specific effector T cells.Fil: Imperato, Jessica Nancy. Stony Brook University Renaissance School Of Medicine; Estados UnidosFil: Xu, Daqi. Uconn Health; Estados UnidosFil: Romagnoli, Pablo Alberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa | Universidad Nacional de Cordoba. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa | Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa.; ArgentinaFil: Qiu, Zhijuan. Stony Brook University Renaissance School Of Medicine; Estados UnidosFil: Perez, Pedro. Stony Brook University Renaissance School Of Medicine; Estados UnidosFil: Khairallah, Camille. Stony Brook University Renaissance School Of Medicine; Estados UnidosFil: Pham, Quynh Mai. Uconn Health; Estados UnidosFil: Andrusaite, Anna. University of Glasgow; Reino UnidoFil: Bravo Blas, Alberto. The Beatson Institute For Cancer Research; Reino UnidoFil: Milling, Simon W. F.. University of Glasgow; Reino UnidoFil: Lefrancois, Leo. Uconn Health; Estados UnidosFil: Khanna, Kamal M.. University of New York; Estados UnidosFil: Puddington, Lynn. Uconn Health; Estados UnidosFil: Sheridan, Brian S.. Stony Brook University Renaissance School Of Medicine; Estados Unido

Dissection of the Role of Pregnane X Receptor in Innate Immunity and Investigation of the CD8+ T Cell Response during Cytomegalovirus Infection and Its Application in Vaccine Development

The pregnane X receptor (PXR), also known as steroid and xenobiotic receptor, pregnane activated receptor or NR1l2, is a nuclear receptor that is highly expressed in the intestine and liver and plays a critical role in regulating xenobiotic metabolisom. Recent studies have suggested that PXR cross talks with NF-κB signaling pathway in intestinal epithelial cells and hepatocytes and therefore regulates inflammation in the intestine and liver. However, its role in the immune system is not known. In Chapter III, We defined a novel hematopoietic intrinsic role for PXR as a critical regulator of pathogen-induced inflammation and host defense against microbial infection by modulating the toll-like receptor 4 (TLR4) signaling pathway. Our study suggests that PXR can be a novel pharmaceutical target for inflammatory diseases. CD8+ T cells are effective for tumor rejection. The presence of tumor infiltrating CD8+ T cells is associated with tumor regression and better prognosis. Cytomegalovirus (CMV) infection elicits a robust and long-lasting CD8+ T cell response, which makes CMV a potentially promising vaccine vector against cancer. In Chapter IV, we constructed a CMV-based cancer vaccine by engineering CMV to express a modified tumor antigen. We demonstrated that immunization with this vaccine was effective in overcoming the immune suppressive environment and the immune tolerance to tumor antigens and induced robust antitumoral CD8+ T cells, which resulted in subsequent tumor regression. Our study suggests that CMV is a promising vaccine vector to prevent and treat cancers. CMV is an opportunistic pathogen that can cause serious diseases in individuals with an immature or compromised immune system. CMV infection induces potent CD8+ T cell responses that increase with age, a phenomenon called “memory inflation”. These CD8+ T cells are central to controlling viral reactivation. In Chapter V, we demonstrated that antigens were constantly presented to CD8+ T cells, which likely drove the inflationary CD8+ T cell response. The inflationary CD8+ T cell pool sustained without the replenishment of naïve T cells. Furthermore, these inflationary CD8+ T cells expressed few inhibitory molecules and maintained polyfunctional during latency. Our study has important implications for the development of T cell based anti-CMV vaccines

Listeria Monocytogenes: A Model Pathogen Continues to Refine Our Knowledge of the CD8 T Cell Response

Listeria monocytogenes (Lm) infection induces robust CD8 T cell responses, which play a critical role in resolving Lm during primary infection and provide protective immunity to re-infections. Comprehensive studies have been conducted to delineate the CD8 T cell response after Lm infection. In this review, the generation of the CD8 T cell response to Lm infection will be discussed. The role of dendritic cell subsets in acquiring and presenting Lm antigens to CD8 T cells and the events that occur during T cell priming and activation will be addressed. CD8 T cell expansion, differentiation and contraction as well as the signals that regulate these processes during Lm infection will be explored. Finally, the formation of memory CD8 T cell subsets in the circulation and in the intestine will be analyzed. Recently, the study of CD8 T cell responses to Lm infection has begun to shift focus from the intravenous infection model to a natural oral infection model as the humanized mouse and murinized Lm have become readily available. Recent findings in the generation of CD8 T cell responses to oral infection using murinized Lm will be explored throughout the review. Finally, CD8 T cell-mediated protective immunity against Lm infection and the use of Lm as a vaccine vector for cancer immunotherapy will be highlighted. Overall, this review will provide detailed knowledge on the biology of CD8 T cell responses after Lm infection that may shed light on improving rational vaccine design

TGF-β: Many Paths to CD103+ CD8 T Cell Residency

CD8 tissue-resident memory T (TRM) cells primarily reside in nonlymphoid tissues without recirculating and provide front-line protective immunity against infections and cancers. CD8 TRM cells can be generally divided into CD69+ CD103− TRM cells (referred to as CD103− TRM cells) and CD69+ CD103+ TRM cells (referred to as CD103+ TRM cells). TGF-β plays a critical role in the development and maintenance of CD103+ CD8 TRM cells. In this review, we summarize the current understanding of tissue-specific activation of TGF-β mediated by integrins and how it contributes to CD103+ CD8 TRM cell development and maintenance. Furthermore, we discuss the underlying mechanisms utilized by TGF-β to regulate the development and maintenance of CD103+ CD8 TRM cells. Overall, this review highlights the importance of TGF-β in regulating this unique subset of memory CD8 T cells that may shed light on improving vaccine design to target this population

Combining Adoptive Cell Therapy with Cytomegalovirus-Based Vaccine Is Protective against Solid Skin Tumors

Despite many years of research, cancer vaccines have largely been ineffective in the treatment of established cancers. Many barriers to immune-mediated destruction of malignant cells exist, and these likely limit the efficacy of cancer vaccines. In this study, we sought to enhance the efficacy of a cytomegalovirus (CMV)-based vaccine targeting melanoma by combining vaccination with other forms of immunotherapy. Adoptive cell therapy in humans and in animal models has been shown to be effective for tumor regression. Thus, in this study, we assessed whether CMV-based vaccines in combination with adoptively transferred antitumor T cells could provide greater antitumor protection than either therapy alone. Our results show that adoptive cell therapy greatly enhanced the antitumor effects of CMV-based vaccines targeting the foreign model antigen, OVA, or the melanoma differentiation antigen, gp100. Combination adoptive cell therapy and vaccination induced the upregulation of the inhibitory ligands, PD-L1, and Qa-1b, on B16 tumor cells. This expression paralleled the infiltration of tumors by vaccine-stimulated T cells which also expressed high levels of the receptors PD-1 and NKG2A/C/E, suggesting a potential mechanism of tumor immune evasion. Surprisingly, therapeutic blockade of the PD-1/PD-L1 and NKG2A/Qa-1b axes did not delay tumor growth following vaccination, suggesting that the presence of inhibitory ligands within malignant tissue may not be an effective biomarker for successful combination therapy with CMV-based vaccines. Overall, our studies show that therapeutic CMV-based vaccines in combination with adoptive T cell transfer alone are effective for tumor rejection

Autographa californica Multicapsid Nucleopolyhedrovirus Efficiently Infects Sf9 Cells and Transduces Mammalian Cells via Direct Fusion with the Plasma Membrane at Low pH▿

The budded virus (BV) of the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) infects insect cells and transduces mammalian cells mainly through the endocytosis pathway. However, this study revealed that the treatment of the virus bound to Sf9 cells at low pH could efficiently rescue the infectivity of AcMNPV in the presence of endocytosis pathway inhibitors. A colocalization assay of the major capsid protein VP39 with the early endosome marker EEA1 showed that at low pH, AcMNPV entered Sf9 cells via an endosome-independent pathway. Using a fluorescent probe (R18), we showed that at low pH, the viral nucleocapsid entered Sf9 cells via direct fusion at the cell surface. By using the myosin-specific inhibitor 2,3-butanedione monoxime (BDM) and the microtubule inhibitor nocodazole, the low pH-triggered direct fusion was demonstrated to be dependent on myosin-like proteins and independent of microtubules. The reverse transcription-PCR of the IE1 gene as a marker for viral entry showed that the kinetics of AcMNPV in cells triggered by low pH was similar to that of the normal entry via endocytosis. The low pH-mediated infection assay and VP39 and EEA1 colocalization assay also demonstrated that AcMNPV could efficiently transduce mammalian cells via direct membrane fusion at the cell surface. More importantly, we found that a low-pH trigger could significantly improve the transduction efficiency of AcMNPV in mammalian cells, leading to the potential application of this method when using baculovirus as a vector for heterologous gene expression and for gene therapy