TNF is important for pathogen control and limits brain damage in murine cerebral listeriosis.

Cerebral listeriosis is a life-threatening disease. However, little is known about the bacterial virulence factors responsible for the severe course of disease and the factors of the immune system contributing to the control of Listeria monocytogenes (LM) or even to the damage of the brain. To analyze the importance of the actA gene of LM, which mediates cell-to-cell spread of intracellular LM, the function of TNF in murine cerebral listeriosis was studied.

Making sense of inflammation, epigenetics, and memory CD8+ T-cell differentiation in the context of infection.

Recent findings suggest a new paradigm that early inflammatory cytokines promote the effector T-cell response while inhibiting the development of CD8+ T-cell memory. Although this opposing effect may appear paradoxical at first, it makes biological sense in the context of an infection, by ensuring a maximal effector response that will clear the pathogen. Once infection is controlled, the withdrawal of inflammatory cytokines allows the differentiation of effectors into long-lived memory cells that provide protective immunity against re-infection.

Epigenetic remodeling of the IL-2 and IFN-gamma loci in memory CD8 T cells is influenced by CD4 T cells.

Memory T cells (T(M)) are able to rapidly exert effector functions, including immediate effector cytokine production upon re-encounter with Ag, which is critical for protective immunity. Furthermore, this poised state is maintained as T(M) undergo homeostatic proliferation over time. We examined the molecular basis underlying this enhanced functional capacity in CD8 T(M) by comparing them to defective CD8 T(M) generated in the absence of CD4 T cells.

Clonal competition inhibits the proliferation and differentiation of adoptively transferred TCR transgenic CD4 T cells in response to infection.

CD4 and CD8 T cells have been shown to proliferate and differentiate to different extents following antigenic stimulation. CD4 T cells form a heterogenous pool of effector cells in various stages of division and differentiation, while nearly all responding CD8 T cells divide and differentiate to the same extent. We examined CD4 and CD8 T cell responses during bacterial infection by adoptive transfer of CFSE-labeled monoclonal and polyclonal T cells.

Impaired protection against Mycobacterium bovis bacillus Calmette-Guerin infection in IL-15-deficient mice.

To investigate the potential role of endogenous IL-15 in mycobacterial infection, we examined protective immunity in IL-15-deficient (IL-15(-/-)) mice after infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) or recombinant OVA-expressing BCG (rBCG-OVA). IL-15(-/-) mice exhibited an impaired protection in the lung on day 120 after BCG infection as assessed by bacterial growth. CD4(+) Th1 response capable of producing IFN-gamma was normally detected in spleen and lung of IL-15(-/-) mice on day 120 after infection.

Inducible nitric oxide synthase mediates prostaglandin h2 synthase nitration and suppresses eicosanoid production.

Nitric oxide (NO) modulates the biological levels of arachidonate-derived cell signaling molecules by either enhancing or suppressing the activity of prostaglandin H(2) isoforms (PGHS-1 and PGHS-2). Whether NO activates or suppresses PGHS activity is determined by alternative protein modifications mediated by NO and NO-derived species. Here, we show that inducible NO synthase (iNOS) and PGHS-1 co-localize in atherosclerotic lesions of ApoE(-/-) mouse aortae.

IL-15 regulates CD8+ T cell contraction during primary infection.

During the course of acute infection with an intracellular pathogen, Ag-specific T cells proliferate in the expansion phase, and then most of the T cells die by apoptosis in the following contraction phase, but the few that survive become memory cells and persist for a long period of time. Although IL-15 is known to play an important role in long-term maintenance of memory CD8+ T cells, the potential roles of IL-15 in CD8+ T cell contraction are not known. Using an adoptive transfer system of OT-I cells expressing OVA257-264/Kb-specific TCR into control, IL-15 knockout (KO) and IL-15 transgenic (Tg) mice followed by challenge with recombinant Listeria monocytogenes expressing OVA, we found that the survival of CD44+CD62L-CD127- effector OT-I cells during the contraction phase is critically dependent on IL-15.

SARS vaccine: progress and challenge.

Severe acute respiratory syndrome (SARS) emerged in 2002 as a severe and highly contagious infectious disease that rapidly spread to a number of different countries. The collaborative efforts of the global scientific community have provided, within a short period of time, substantial insights into the molecular biology and immunology of SARS-CoV. Although the outbreak has been contained, there is continuous concern that the virus may resurface into the human population through seasonal changes, animal reservoirs or laboratory accidents.

Characterization of Listeria monocytogenes expressing anthrolysin O and phosphatidylinositol-specific phospholipase C from Bacillus anthracis.

Two virulence factors of Listeria monocytogenes, listeriolysin O (LLO) and phosphatidylinositol-specific phospholipase C (PI-PLC), mediate escape of this pathogen from the phagocytic vacuole of macrophages, thereby allowing the bacterium access to the host cell cytosol for growth and spread to neighboring cells. We characterized their orthologs from Bacillus anthracis by expressing them in L. monocytogenes and characterizing their contribution to bacterial intracellular growth and cell-to-cell spread.

Bordetella type III secretion modulates dendritic cell migration resulting in immunosuppression and bacterial persistence.

Chronic bacterial infection reflects a balance between the host immune response and bacterial factors that promote colonization and immune evasion. Bordetella bronchiseptica uses a type III secretion system (TTSS) to persist in the lower respiratory tract of mice. We hypothesize that colonization is facilitated by bacteria-driven modulation of dendritic cells (DCs), which leads to an immunosuppressive adaptive host response.

Electro-optic polymer waveguide grating with fast tuning capability.

A novel fast tunable electro-optic (EO) polymer waveguide grating is proposed and designed. Its resonant wavelength can be linearly tuned via the first-order EO effect with a high sensitivity of 6.1 pm/V.

Phosphatidylinositol-specific phospholipase C of Bacillus anthracis down-modulates the immune response.

Phosphatidylinositol-specific phospholipases (PI-PLCs) are virulence factors produced by many pathogenic bacteria, including Bacillus anthracis and Listeria monocytogenes. Bacillus PI-PLC differs from Listeria PI-PLC in that it has strong activity for cleaving GPI-anchored proteins. Treatment of murine DCs with Bacillus, but not Listeria, PI-PLC inhibited dendritic cell (DC) activation by TLR ligands.

In vivo modulation of T cell responses and protective immunity by TCR antagonism during infection.

Infectious agents are known to express altered peptide ligands that antagonize T cells in vitro; however, direct evidence of TCR antagonism during infection is still lacking, and its importance in the context of infection remains to be established. In this study, we used a murine model of infection with recombinant Listeria monocytogenes and addressed three issues that are critical for assessing the role of TCR antagonism in the modulation of the immune response. First, we demonstrated that the antagonist peptide efficiently inhibited the ability of the agonist to prime naive TCR-transgenic T cells in vivo.

In vitro cell response to a polymer surface micropatterned by laser interference lithography.

This presentation will introduce laser interference lithography to prepare a periodic line and point micropatterns for study of cell-surface interactions. This process provides a straightforward micropatterning technique based on selective laser ablation of polymers utilizing the periodic energy distribution of two or more beam interference patterns. The micropatterns were characterized by atomic force microscopy, while the surface chemical modification was analyzed using X-ray photoelectron spectroscopy.

Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein.

The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). CD8 T cells play an important role in controlling diseases caused by other coronaviruses and in mediating vaccine-induced protective immunity in corresponding animal models. The spike protein, a main surface antigen of SARS-CoV, is one of the most important antigen candidates for vaccine design.

Influence of the obligate parasite Cuscuta campestris on growth and biomass allocation of its host Mikania micrantha.

As a means of biologically controlling Mikania micrantha H.B.K.

A novel role of IL-15 in early activation of memory CD8+ CTL after reinfection.

A rapid induction of effector functions in memory T cells provides rapid and intensified protection against reinfection. To determine potential roles of IL-15 in early expansion and activation of memory CD8+ T cells in secondary immune response, we examined the cell division and cytotoxicity of memory CD8+ T cells expressing OVA(257-264)/Kb-specific TCR that were transferred into IL-15-transgenic (Tg) mice, IL-15 knockout (KO) mice, or control C57BL/6 mice followed by challenge with recombinant Listeria monocytogenes expressing OVA (rLM-OVA). In vivo CTL activities and expression of granzyme B of the transferred CD8+ T cells were significantly higher in the IL-15 Tg mice but lower in the IL-15 KO mice than those in control mice at the early stage after challenge with rLM-OVA.

Recent immune status determines the source of antigens that drive homeostatic T cell expansion.

Homeostatic proliferation of naive T cells transferred to T cell-deficient syngeneic mice is driven by low-affinity self-MHC/peptide ligands and the cytokine IL-7. In addition to homeostatic proliferation, a subset of naive T cells undergoes massive proliferation in chronically immunodeficient hosts, but not in irradiated normal hosts. Such rapid T cell proliferation occurs largely independent of homeostatic factors, because it was apparent in the absence of IL-7 and in T cell-sufficient hosts devoid of functional T cell immunity.

Increased epitope-specific CD8+ T cells prevent murine coronavirus spread to the spinal cord and subsequent demyelination.

CD8+ T cells are important for clearance of neurotropic mouse hepatitis virus (MHV) strain A59, although their possible role in A59-induced demyelination is not well understood. We developed an adoptive-transfer model to more clearly elucidate the role of virus-specific CD8+ T cells during the acute and chronic phases of infection with A59 that is described as follows. C57BL/6 mice were infected with a recombinant A59 virus expressing the gp33 epitope, an H-2Db-restricted CD8+ T-cell epitope encoded in the glycoprotein of lymphocytic choriomeningitis virus, as a fusion with the enhanced green fluorescent protein (RA59-gfp/gp33).

Laser interference lithography as a new and efficient technique for micropatterning of biopolymer surface.

Laser interference lithography (LIL) is a straightforward technique to prepare linear micropatterns for regulating cellular adhesion behaviors on polymer substratum. This process is based on selective laser ablation directly duplicating the interference patterns of two or more coherent laser beams onto the polymer surface. Micropatterns prepared by LIL on poly(ethylene terephthalate) and Thermanox were characterized using atomic force microscopy (AFM) and white light interferometer while the chemical surface modification induced by laser was analyzed by X-ray photoelectron spectroscopy (XPS).

Reduced apoptosis and ameliorated listeriosis in TRAIL-null mice.

Listeriosis is an infectious disease caused by the bacterium Listeria monocytogenes. Although it is well recognized that apoptosis plays a critical role in the pathogenesis of the disease, the molecular mechanisms of cell death in listeriosis remain to be established. We report in this study that mice deficient in TRAIL were partially resistant to primary listeriosis, and blocking TRAIL with a soluble death receptor 5 markedly ameliorated the disease.

[Effects of kidney-tonifying Chinese herbal medicine on hypothalamic-pituitary gonadotrophic function].

Objective: To observe the effects of kidney-tonifying Chinese herbal medicine on the synthesis and secretion of gonadotropin releasing hormone (GnRH) and the related neurotransmitters and neuropeptides, and to explore the mechanism of the regulative effect of Chinese herbal medicine on the hypothalamic-pituitary gonadotrophic function.

Methods: Female Sprague-Dawley rats during the period of normal adolescent initiation (160-180 g, 1.5 months) were randomly divided into three groups.

Functional characterization of MHC class II-restricted CD8+CD4- and CD8-CD4- T cell responses to infection in CD4-/- mice.

Classical CD4(+) and CD8(+) T cells recognize Ag presented by MHC class II (MHCII) and MHC class I (MHCI), respectively. However, our results show that CD4(-/-) mice mount a strong, readily detectable CD8(+) T cell response to MHCII-restricted epitopes after a primary bacterial or viral infection. These MHCII-restricted CD8(+)CD4(-) T cells are more similar to classical CD8(+) T cells than to CD4(+) T cells in their expression of effector functions during a primary infection, yet they also differ from MHCI-restricted CD8(+) T cells by their inability to produce high levels of the cytolytic molecule granzyme B.

Bordetella type III secretion and adenylate cyclase toxin synergize to drive dendritic cells into a semimature state.

Bordetella bronchiseptica establishes persistent infection of the murine respiratory tract. We hypothesize that long-term colonization is mediated in part by bacteria-driven modulation of dendritic cells (DCs) leading to altered adaptive immune responses. Bone marrow-derived DCs (BMDCs) from C57BL/6 mice infected with live B.

CD8+ T-cell memory: only the good ones last.

Generating long-lasting, protective CD8(+) T-cell memory via vaccination is critical for combating infectious diseases. Advances in the past year have provided many new insights into how memory CD8(+) T cells are generated. It is now recognized that CD8(+) T cells differentiate from 'effector memory' cells into 'central memory' cells, which are stably maintained and confer superior protective immunity.