Outer Membrane Protein of Gut Commensal Microorganism Induces Autoantibody Production and Extra-Intestinal Gland Inflammation in Mice.

Gut commensal microorganisms have been linked with chronic inflammation at the extra-intestinal niche of the body. The object of the study was to investigate on the chronic effects of a gut commensal on extra-intestinal glands. The presence of autoimmune response was diagnosed by autoantibody levels and histological methods.

Impact of the Timing of Morphine Administration on Lipopolysaccharide-Mediated Lethal Endotoxic Shock in Mice.

Sepsis is a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of the cytokine storm caused by dysregulation of cytokine production. Morphine influences the severity of infection in vivo and in vitro because it regulates cytokine production.

Staphylococcal enterotoxin B toxic shock syndrome induced by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).

We herein report a case of toxic shock syndrome (TSS) associated with the 2009 pandemic H1N1 (pH1N1) influenza virus and a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in a 16-year-old Vietnamese girl. Staphylococcal enterotoxin B (SEB) was detected in the patient's serum, and the level of anti-SEB antibodies was found to be elevated. A flow cytometric analysis showed evidence of activated SEB-reactive Vβ3+ and Vβ12+ T cells.

Plasma leukocyte cell-derived chemotaxin 2 is associated with the severity of systemic inflammation in patients with sepsis.

The aim of the present study was to determine the correlations between leukocyte cell-derived chemotaxin 2 (LECT2) and inflammation-related variables in human inflammatory disease. Plasma samples from 23 septic patients who had been admitted to the intensive care unit (ICU) of our institution and 31 volunteers were used. Plasma LECT2 concentrations were examined retrospectively and compared with those of various inflammatory cytokines and routine laboratory data.

Involvement of commensal bacteria may lead to dysregulated inflammatory and autoimmune responses in a mouse model for chronic nonsuppurative destructive cholangitis.

Background: We previously reported a mouse model of primary biliary cirrhosis (PBC)-like chronic nonsuppurative destructive cholangitis (CNSDC), in which frequent injections of Streptococcus intermedius induced CNSDC and autoantibody production. The present study was performed to verify the model by examining 1) the reappearance of the PBC-like CNSDC after lymphocyte transfer from model to naïve mice, 2) the involvement of autophagy, and 3) the influence of the strain difference.

Methods: Mice were inoculated with S.

Possible role of LECT2 as an intrinsic regulatory factor in SEA-induced toxicity in d-galactosamine-sensitized mice.

To elucidate whether leukocyte cell-derived chemotaxin 2 (LECT2) controls the progression of staphylococcal enterotoxin A (SEA)-induced toxicity, we examined the role of LECT2 in a mouse model. Almost all the C57BL/6J (B6) mice survived for 72 h after the injection of 0.1 μg of SEA and 20 mg of d-galactosamine (d-GalN).

A mouse model of autoimmune pancreatitis with salivary gland involvement triggered by innate immunity via persistent exposure to avirulent bacteria.

The pathogenesis of autoimmune pancreatitis (AIP) remains unknown. Here, we investigated the possible involvement of chronic, persistent exposure to avirulent bacteria in the pathogenesis of AIP. C57BL/6 mice were inoculated with heat-killed Escherichia coli weekly for 8 weeks.

High affinity of interaction between superantigen and T cell receptor Vbeta molecules induces a high level and prolonged expansion of superantigen-reactive CD4+ T cells.

In mice implanted with an osmotic pump filled with the superantigen (SAG) staphylococcal enterotoxin A (SEA), the Vβ3(+)CD4(+) T cells exhibited a high level of expansion whereas the Vβ11(+)CD4(+) T cells exhibited a mild level of expansion. In contrast, in mice implanted with an osmotic pump filled with SE-like type P (SElP, 78.1% homologous with SEA), the Vβ11(+)CD4(+) T cells exhibited a high level of expansion while the Vβ3(+)CD4(+) T cells exhibited a low level of expansion, suggesting that the level of the SAG-induced response is determined by the affinities between the TCR Vβ molecules and SAG.

Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation.

Bacterial infection has become a focus of attention in the pathogenesis of primary biliary cirrhosis (PBC). We earlier reported that the bacterial lipoteichoic acid was detected at the sites of inflammation around damaged bile ducts in the livers of PBC, and PBC patients' sera showed high titers against streptococcal histone-like protein. Here, we investigated whether chronic bacterial exposure could trigger PBC-like epithelial cell damage in normal mouse.

T cell activation in abnormal perinatal events.

The aim of this study was to determine the percentage of CD45RO(+) T cells in umbilical cord blood from neonates born at less than 37 weeks of gestation. Fifty-nine patients were enrolled in this study, including 49 with preterm and 10 with term deliveries. Preterm deliveries were divided into two categories; spontaneous (Group A, n= 31) and indicated (Group B, n= 18).

Change of specific T cells in an emerging neonatal infectious disease induced by a bacterial superantigen.

A new epidemic, NTED, has recently occurred in Japan. The cause of NTED is a bacterial superantigen, TSST-1. The aim of the present study was to analyze the change in Vbeta2(+) T cells reactive to TSST-1 in NTED in order to establish T-cell-targeted diagnostic criteria for NTED.

Diagnosis of toxic shock syndrome by two different systems; clinical criteria and monitoring of TSST-1-reactive T cells.

Two methods of TSS diagnosis were evaluated: comparison of symptoms with clinical criteria and monitoring for evidence of selective activation of Vbeta2(+) T cells by the causative toxin, TSS toxin-1 (TSST-1). Ten patients with acute and systemic febrile infections caused by Staphylococcus aureus were monitored for increase in TSST-1-reactive Vbeta2(+) T cells during their clinical courses. Nine of the ten patients were diagnosed with TSS based on evidence of selective activation of Vbeta2(+) T cells by TSST-1; however, clinical symptoms met the clinical criteria for TSS in only six of these nine patients.

Identification and characterization of two novel staphylococcal enterotoxins, types S and T.

In addition to two known staphylococcal enterotoxin-like genes (selj and selr), two novel genes coding for two superantigens, staphylococcal enterotoxins S and T (SES and SET), were identified in plasmid pF5, which is harbored by food poisoning-related Staphylococcus aureus strain Fukuoka 5. This strain was implicated in a food poisoning incident in Fukuoka City, Japan, in 1997. Recombinant SES (rSES) specifically stimulated human T cells in a T-cell receptor Vbeta9- and Vbeta16-specific manner in the presence of major histocompatibility complex (MHC) class II(+) antigen-presenting cells (APC).

A possible role of histone-like DNA-binding protein of Streptococcus intermedius in the pathogenesis of bile duct damage in primary biliary cirrhosis.

Bacterial infection has become a focus of attention in the pathogenesis of primary biliary cirrhosis (PBC). It was reported that anti-histone autoantibody was detected in PBC, suggesting that bacterial histone-like DNA-binding protein (HLP) may be involved in the pathogenesis of PBC. To identify bacterial species in PBC to confirm this possibility, serum reactivity to bacterial cells was studied by ELISA.

Crystal structure of Streptococcus dysgalactiae-derived mitogen reveals a zinc-binding site and alterations in TcR binding.

Bacterial superantigens are protein toxins with an ability to cause serious diseases in humans by activating a large number of T cells. Streptococcus dysgalactiae-derived mitogen (SDM) is a novel superantigen that is distinct from other known superantigens based on phylogenetic analysis. The X-ray structure of SDM has been determined at 1.

Cloning, expression, and characterization of the superantigen streptococcal pyrogenic exotoxin G from Streptococcus dysgalactiae.

We identified seven novel variants of streptococcal pyrogenic exotoxin G (SPEGG), a superantigen, in Streptococcus dysgalactiae subsp. dysgalactiae or equisimilis isolates from clinical cases of infection in humans and animals. Phylogenetic analysis of the SPEGG variants indicated two clades in the dendrogram: one composed of variants derived from the bacteria isolated from the humans and the other composed of variants from the bacteria isolated from the animals.

A severe case of neonatal toxic shock syndrome-like exanthematous disease with superantigen-induced high T cell response.

Most newborn patients with a neonatal type of toxic shock syndrome (TSS), called neonatal TSS-like exanthematous disease (NTED), exhibit mild clinical symptoms. We present the case of a patient with NTED who exhibited exceptionally severe clinical symptoms and an adult-type T cell response to the causative toxin TSS toxin-1.

Lipoteichoic acid may affect the pathogenesis of bile duct damage in primary biliary cirrhosis.

Aim: Intrahepatic bile ducts are the targets for inflammation in primary biliary cirrhosis (PBC), but their pathogenesis is not known. Gram-positive bacterial DNA was detected recently in gallbladder bile of PBC patients. In the present study, we assessed the possible pathological role of lipoteichoic acid (LTA), the gram-positive bacterial cell wall component, in PBC.

Expression, purification and crystallization of Streptococcus dysgalactiae-derived mitogen.

Superantigens are bacterial or viral toxins with potent immunostimulatory properties. Streptococcus dysgalactiae-derived mitogen, a 25 kDa protein, is a recently discovered superantigen isolated from S. dysgalactiae culture supernatant.

Characterization of novel staphylococcal enterotoxin-like toxin type P.

We investigated the biological properties of a novel staphylococcal enterotoxin (SE)-like toxin type P (SElP). SElP induced a substantial proliferative response and the production of cytokines interleukin-2, gamma interferon, tumor necrosis factor alpha, and interleukin-4 from human T cells when administered at a concentration of 0.4 pM (0.

Studies of recombinant streptococcal pyrogenic exotoxin B/cysteine protease (rSPE B/SCP) in the skin of guinea pigs & the release of histamine from cultured mast cells & basophilic leukocytes.

Background & Objectives: Streptococcal pyrogenic exotoxin B/streptococcal cysteine protease (SPE B/SCP) is considered to be one of the virulence factors of Streptococcus pyogenes (S. pyogenes) which causes serious diseases such as severe invasive infections and streptococcal toxic shock syndrome (STSS). There are no reports on the histamine releasing activity of SPE B/SCP from mast cells, although several biological activities have been studied.

Biological properties of staphylococcal enterotoxin-like toxin type R.

We investigated the biological properties of a novel staphylococcal enterotoxin-like putative toxin, staphylococcal enterotoxin-like toxin type R (SElR). Major histocompatibility complex class II molecules were required for T-cell stimulation by SElR. SElR stimulated T cells bearing receptors Vbeta 3, 11, 12, 13.

Immunologic immaturity, but high IL-4 productivity, of murine neonatal thymic CD4 single-positive T cells in the last stage of maturation.

To determine the levels of maturation and differentiation of murine CD4 single-positive (SP) T cells, we compared the secondary responses of staphylococcal enterotoxin A (SEA)-induced neonatal thymic, adult thymic and adult splenic CD4 SP T cell blasts prepared from whole or heat-stable antigen(low) CD4 SP T cells. Proliferative responses upon re-stimulation with SEA were strong in adult splenic CD4 SP T cell blasts, but quite weak in neonatal thymic and adult thymic CD4 SP T cell blasts. SEA-induced IL-2 production was weaker in neonatal thymic blasts than in the adult splenic CD4 SP T cell blasts.

Akt is a neutral amplifier for Th cell differentiation.

Both CD28 and its relative, inducible costimulator (ICOS), have a binding motif for phosphatidylinositol 3-kinase (PI3K) in their cytoplasmic tail, and the binding of PI3K leads to activation of a serine/threonine kinase, Akt. The role of Akt in cytokine production and helper T (Th) cell differentiation remains obscure. In this study, we found that enforced expression of the constitutively active form (E40K) of Akt rendered CD4(+) T cells activated.

Maturation of adult peripheral blood CD38(+)CD4(+) T cells demonstrated by cytokine production in response to a superantigen, TSST-1.

This study looks at immunoincompetent CD4(+) T cells in adult peripheral blood (APB) using cytokine production in response to a superantigen as a measure of function. We compared the function of APB CD38(+)CD4(+) and CD38(-/low)CD4(+) T cells to that of cord blood (CB) CD4(+) T cells. APB CD4(+) T cell blasts produce substantial amounts of IL-2 in response to TSST-1 restimulation, while CB CD4(+) T cell blasts produce less.