Search

Circulating memory CD8 T cell trafficking and protective capacity during liver-stage malaria infection remains undefined. We find that effector memory CD8 T cells (Tem) infiltrate the liver within 6 hours after malarial or bacterial infections and mediate pathogen clearance. Tem recruitment coincides with rapid transcriptional upregulation of inflammatory genes in Plasmodium-infected livers. Recruitment requires CD8 T cell-intrinsic LFA-1 expression and the presence of liver phagocytes. Rapid Tem liver infiltration is distinct from recruitment to other non-lymphoid tissues in that it occurs both in the absence of liver tissue resident memory "sensing-and-alarm" function and ∼42 hours earlier than in lung infection by influenza virus. These data demonstrate relevance for Tem in protection against malaria and provide generalizable mechanistic insights germane to control of liver infections., Competing Interests: Declarations of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Infection due to Listeria monocytogenes (LM) is rare in neonates; thus, its clinical presentation and outcomes are not commonly reported, especially in low- and middle-income countries. In 2017, South Africa had an outbreak due to LM., Objective: To determine demographic characteristics, clinical and laboratory findings and outcomes of all neonates infected with LM during the outbreak period., Methods: This is a retrospective analytic study. Clinical and laboratory records of neonates admitted at Chris Hani Baragwanath Academic Hospital from January 2017 to May 2018 with positive blood and cerebrospinal fluid culture with LM were reviewed for demographic characteristics, clinical presentation, ancillary laboratory test results and outcomes at hospital discharge., Results: There were 42 neonates with positive cultures due to LM. Thirty-four (81%) were born preterm. Mode of delivery was vaginal in 78.6% and 31.0% were HIV exposed. All patients presented within the first 6 days of life as an early-onset disease. Common clinical presentation was respiratory depression (52.4%) and respiratory distress (38.1%) with 69% requiring invasive or noninvasive respiratory support. Common abnormal laboratory findings were high C-reactive protein (77.1%) followed by leukopenia (23.8%). Fourteen patients (40%) had features of meningitis based on blood and cerebrospinal fluid findings (4 culture proven). There were 11 deaths at hospital discharge, giving a mortality rate of 26.2%., Conclusions: The majority of neonates infected with LM were born preterm, raising the possibility that LM itself may have been responsible for preterm labor. All presented in the first 6 days of life and most presented with respiratory distress or depression. A high proportion had meningitis, and there was a high-mortality overall., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The present study evaluated the comparative serodiagnostic efficacy of recombinant listeriolysin-O (rLLO) and synthetic LLO- 2 peptide-based indirect ELISA vis-à-vis cultural isolation using samples (n = 1326; blood, sera, vaginal swabs, and rectal swabs) collected from caprines (n = 350) and ovines (n = 50) having reproductive and/or nervous system disorders and/or healthy animals. On screening the test sera by rLLO- based ELISA, the antibodies against LLO (ALLO) were observed in 17.71% of the caprines and 2% of the ovines, respectively, while synthetic LLO-2- based ELISA revealed ALLO in 6.86% of caprines and not in ovines. Moreover, the adsorption of positive test sera with streptolysin-O (SLO) resulted in a significant reduction (7.43%; p < 0.05) in the seropositivity with rLLO- based ELISA, whereas LLO-2- based ELISA revealed marginal reduction (4.29%; p > 0.05) in the seropositivity. Overall, the seropositivity with LLO-2 synthetic peptide revealed comparatively less cross-reactivity in comparison to rLLO. The cultural isolation yielded five pathogenic L. monocytogenes isolates and three non-pathogenic Listeria spp. from caprine samples; however, Listeria spp. could not be recovered from any of the ovine samples. Further, on comparing seropositivity with the isolation study results, it was found that two out of the five animals from which pathogenic L. monocytogenes isolated were also found seropositive in both the ELISAs even after adsorption with SLO. Interestingly, rLLO- based ELISA detected antibodies against unadsorbed caprine sera even in those samples from which non-pathogenic Listeria spp. were isolated, whereas antibodies were not detected in LLO-2 peptide-based ELISA. In conclusion, it could be inferred that the synthetic LLO-2 peptide serves as a non- cross-reactive, ideal diagnostic antigen in serodiagnosis of capro-ovine listeriosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We reviewed 18 listeriosis cases in Japan and performed molecular analysis of causative Listeria monocytogenes (LM) isolates. Strains genetically related to those from other countries caused various types of listeriosis, including vascular listeriosis in immunocompetent elderly people. Our results highlight the importance of integrated clinical and genomic analysis of LM., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bacterial growth in the blood and thus have been linked to immunocompromise. In contrast, cell-to-cell spread within nerves is thought to be mediated by a particular subset of neurotropic L. monocytogenes strains. In this study, we used a mouse model of foodborne transmission to evaluate the neurotropism of several L. monocytogenes isolates. Two strains preferentially colonized the brain stems of BALB/cByJ mice 5 days postinfection and were not detectable in blood at that time point. In contrast, infection with other strains resulted in robust systemic infection of the viscera but no dissemination to the brain. Both neurotropic strains (L2010-2198, a human rhombencephalitis isolate, and UKVDL9, a sheep brain isolate) typed as phylogenetic lineage III, the least characterized group of L. monocytogenes Neither of these strains encodes InlF, an internalin-like protein that was recently shown to promote invasion of the blood-brain barrier. Acute neurologic deficits were observed in mice infected with the neurotropic strains, and milder symptoms persisted for up to 16 days in some animals. These results demonstrate that neurotropic L. monocytogenes strains are not restricted to any one particular lineage and suggest that the foodborne mouse model of listeriosis can be used to investigate the pathogenic mechanisms that allow L. monocytogenes to invade the brain stem. IMPORTANCE Progress in understanding the two naturally occurring central nervous system (CNS) manifestations of listeriosis (meningitis/meningoencephalitis and rhombencephalitis) has been limited by the lack of small animal models that can readily distinguish between these distinct infections. We report here that certain neurotropic strains of Listeria monocytogenes can spread to the brains of young otherwise healthy mice and cause neurological deficits without causing a fatal bacteremia. The novel strains described here fall within phylogenetic lineage III, a small collection of L. monocytogenes isolates that have not been well characterized to date. The animal model reported here mimics many features of human rhombencephalitis and will be useful for studying the mechanisms that allow L. monocytogenes to disseminate to the brain stem following natural foodborne transmission., (Copyright © 2020 Senay et al.)

Selectin-ligand interactions are important for leukocyte homing and functionality. The roles of selectin-ligand interactions in modulating immunity to intracellular infections are not completely understood. Mice lacking the expression of fucosyltransferase-IV and -VII (Fucosyltransferase-IV and -VII double knockout, FtDKO) exhibit deficient functionality of selectin-ligand interactions. We addressed the kinetics of infection and immunity to Listeria monocytogenes (LM), an intracellular pathogen, in FtDKO mice. These mice exhibited enhanced ability to clear infection and increased survival to a lethal dose of LM infection relative to wild-type (WT) C57BL/6J controls. This was associated with increased levels of neutrophils, monocytes, and dendritic cells (DCs) in the blood and/or infected organs. Adoptive transfer of bone marrow (BM) cells from FtDKO mice to WT mice resulted in enhanced neutrophil numbers and improved clearance of LM bacteria in recipients. In vivo depletion of myeloid innate immune cells, particularly neutrophils, monocytes, macrophages, and DCs, using anti-Ly-6G (RB6-8C5) monoclonal antibody, reduced the ability of FtDKO mice to curtail LM infection. Nevertheless, depletion using anti-Ly-6G (1A8) known to exclusively deplete neutrophils did not abrogate increased resistance of FtDKO mice to LM infection, suggesting a role for other myeloid innate immune cells in this model. Examination of BM hematopoietic progenitors through flow cytometry and cell culture colony-forming unit assay showed increased frequencies of granulocyte-macrophage progenitors in FtDKO relative to WT mice, Overall, our results indicate that functional selectin ligand deficiency enhances innate immune-mediated resistance to systemic LM infection despite defective leukocyte migration and lymphocyte homing., (©2017 Society for Leukocyte Biology.)

Objective: To analyze the clinical characteristics and perinatal outcomes of listeriosis during pregnancy. Methods: From July 2010 to April 2017, 70 131 women delivered in West China Second University Hospital. Nineteen cases were confirmed as listeriosis. The clinical symptoms, laboratory results, pathogens, placenta pathology and perinatal outcomes were analyzed retrospectively. Results: The median age of the 19 cases was 29.7 (19.0-42.0) years old. The median time before diagnosis was 4.8(0.5-19.0) days. The main clinical symptoms at first visits were high fever (17/19), increased white blood cells (18/19), abdominal pain (12/19). Listeria was found in samples of mother's blood (11/19), vaginal secretions (15/19), placenta (1/19), neonatal blood (4/19), neonatal phlegm (5/19) and neonatal ear secretions (1/19), respectively. Inflammation of placenta was identified in all 19 cases. Among the 19 cases, 1 was grade Ⅰ chorioamnionitis, 4 was grade Ⅱ, 5 was grade Ⅲ and 9 was grade Ⅵ. Only 4 newborn survived after therapy, and others suffered perinatal death, including 8 cases of intrauterine death, 3 cases of miscarriage and 6 cases of treatment failure. Conclusions: Listeriosis has characteristics of acute onset, quick development and high morbidity during pregnancy. The empiric use of antibiotics might not cover listeria. The understanding of listeriosis should be improved.

Objective To illustrate an unusual case of Listeria cerebral abscess. Material and methods A 32-year-old pregnant woman with thrombotic antiphospholipid syndrome (APS) received corticotherapy for two weeks due to hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. After delivery she presented with neurological symptoms and fever. Results The MRI scan confirmed the presence of a brain abscess, and Listeria monocytogenes was isolated in blood cultures. After eight weeks of antibiotic treatment, the patient presented no sequelae. Conclusion L. monocytogenes should be included in the differential diagnosis of patients with fever and neurological dysfunction, especially in those with a recent history of corticotherapy.

The increasing occurrence of multidrug resistant bacteria causing bacteremia infection, constitutes a major health problem, difficult-to-treat bacteremia due to its ability to form biofilm. Buffalo milk lactoperoxidase (BMLpo) is effective and safe to use as bacteriostatic agent. The MIC of BMLpo and amikacin were used to evaluate the antibiofilm activity against resistant L. monocytogenes and S. typhi. Prophylactic effects of BMLpo against L. monocytogenes and S. typhi bacteremia in vivo have been tested and ELISA test used to evaluate serum cytokines. Significant antibiofilm activity of BMLpo observed against the highest biofilm producer isolates. Our results showed that the prophylactic effect of BMLpo in BALB/c mice bacteremic model. A significant clearance of L. monocytogenes and S. typhi, investigated in blood and different organs tissues in BMLpo-treated infected groups when compared to the non-treated groups. Further, analysis of serum cytokines levels revealed that BMLpo prophylaxis modulates their release in different way when it compared to the control. This study showed, BMLpo effects as an alternative antibiofilm agent to compact gram negative pathogens, and protects the host against bacteremia infection. Moreover, the BMLpo role as an immunomodulatory. These investigations indicated the BMLpo crucial role in the practical clinical applications., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A 62-year-old man developed a blood stream infection and meningitis due to Listeria monocytogenes, 20 days after an episode of pseudo-membranous colitis. The patient, hospitalized for the first time for transurethral prostatectomy, was readmitted 20 days later with watery diarrhea. Pseudo-membranous colitis was diagnosed and treated successfully, without testing for Clostridium difficile infection (CDI). After 15 more days, the patient developed again diarrhea, fever and confusion. Hospitalized again, blood and cerebrospinal fluid cultures resulted positive for L. monocytogenes. The patient was treated successfully and a diagnosis of recurrent CDI was confirmed following culture and nucleic acid amplification assays both positive for C. difficile. This is the first report of an invasive listeriosis after CDI underlines the importance of taking greater awareness in complicated blood stream infections that may arise after CDI.

The present study for the first time evaluates the serodiagnostic efficacy of two recombinant antigens namely, listeriolysin O (rLLO) and phosphatidyl-inositol phospholipase C (rPI-PLC). Indirect ELISA with the above recombinant antigens was used on samples collected from bovines (n=106), goats (n=138) and pigs (n=92) having either a history of abortion, emaciation and/or apparently healthy animals. Isolation of Listeria was attempted from the blood samples using USDA-FSIS method. On screening of test sera by rLLO-based ELISA, antibodies against anti-listeriolysin O (ALLO) were observed in goats (22.46%), bovines (15.10%) and pigs (16.31%). As advocated, after adsorption of positive serum samples with streptolysin O (SLO), the seropositivity for ALLO was marginally reduced (p>0.05) in goats (21.73%) and bovines (10.38%), whereas, in pigs the reduction (5.43%) was significant (p<0.05). On the contrary, rPI-PLC-based ELISA revealed higher non-specific seropositivity for antilisterial antibodies in goats (45.65%), bovines (31.13%) and pigs (8.69%). Further, on comparing the seropositivity with isolation rate, of the 16 animals that were culturally-positive for L. monocytogenes, 15 showed ALLO positivity in unadsorbed as well as SLO-adsorbed sera by rLLO-based ELISA, however, rPI-PLC-based ELISA could detect seropositivity in only 5 animals. Moreover, rPI-PLC-based ELISA also showed seropositivity in those animals (7/30) that were culturally positive for other Listeria spp. In conclusion, rLLO can serve as a better antigen than rPI-PLC in ELISA for the serodiagnosis of listeriosis in animals; however, prior adsorption of test sera with SLO is required to avoid false positive results., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Listeria monocytogenes is a Gram-positive intracellular bacterium that was transmitted through contaminated food and causes sepsis and even death. IL-37 has been described as an important anti-inflammatory factor, but little is known about the function of IL-37 in host defense against Liseria monocytogenes (Lm) infection. In mice model of systemic infection, we found that mice treated with IL-37 were more sensitive to Lm infection compared with PBS-treated mice. This reduced resistance to Lm in IL-37-treated mice is accompanied with increased bacterial burden and liver damage. Serum levels of colony-stimulating factors were decreased in IL-37-treated mice. IL-37 treatment reduced bactericidal ability of bone marrow derived macrophages (BMDMs) in vitro, which contribute to the inability of IL-37-treated mice to combat Lm infection. Furthermore, increased apoptosis was observed in Lm-infected macrophages treated with IL-37. Increased macrophage apoptosis reduced percentage in liver macrophages was observed in IL-37-treated mice following Lm infection. These results indicate the negative regulatory effect of IL-37 on host resistance during immune defense against Lm., (Copyright © 2016. Published by Elsevier Inc.)

We characterized incubation periods among outbreak-associated listeriosis cases, using a simulation model to account for patients with multiple exposure dates. The median was 11 days; 90% of cases occurred within 28 days, and incubation periods varied by clinical manifestation., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The cytokine IL-6 is part of a regulatory signaling network that controls immune responses. IL-6 binds either to the membrane-bound IL-6 receptor-α (classic signaling) or to the soluble IL-6 receptor-α (trans-signaling) to initiate signal transduction via gp130 activation. Because classic and trans-signaling of IL-6 fulfill different tasks during immune responses, controlled shedding of the membrane-bound IL-6 receptor-α from the surface of immune cells can be considered a central regulator of IL-6 function. The results from cell culture-based experiments have implicated both a disintegrin and metalloprotease 10 and a disintegrin and metalloprotease 17 in IL-6 receptor-α shedding. However, the nature of the protease mediating IL-6 receptor-α release in vivo is not yet known. We used hypomorphic a disintegrin and metalloprotease 17 mice and conditional a disintegrin and metalloprotease 10 knock-out mice to identify the natural protease of the murine IL-6 receptor-α. Circulating homeostatic soluble IL-6 receptor-α levels are not dependent on a disintegrin and metalloprotease 10 or 17 activity. However, during Listeria monocytogenes infection, IL-6 receptor-α cleavage by the α-secretase a disintegrin and metalloprotease 17 is rapidly induced from the surface of different leukocyte populations. In contrast, CD4-Cre-driven a disintegrin and metalloprotease 10 deletion in T cells did not influence IL-6 receptor-α shedding from these cells after L. monocytogenes infection. A disintegrin and metalloprotease 17 was also required for IL-6 receptor-α ectodomain cleavage and release during endotoxemia. These results demonstrate a novel physiologic role for a disintegrin and metalloprotease 17 in regulating murine IL-6 signals during inflammatory processes., (© Society for Leukocyte Biology.)

We report a unique case of acute bacterial prostatitis probably caused by Listeria monocytogenes in an HIV-infected patient. For the best of our knowledge, this is the first case reported of a patient with this association. Our case illustrates the protean clinical presentations that L. monocytogenes infections may adopt, particularly in immunocompromised patients., (© The Author(s) 2015.)

Objective: This study was conducted to identify the seroprevalance of diseases which are zoonotic and responsible from abortion such as toxoplasmosis, listeriosis and brucellosis in Holstein crossbred cattle of different age and sex in Adana province, between 2008 April-September., Methods: For this purpose, blood serum samples were collected from 132 cattle and analyzed for Toxoplasma gondii, Listeria monocytogenes and Brucella abortus antibodies. T. gondii, L. monocytogenes and Brucella abortus antibodies were determined by the standard Sabin- Feldman Dye Test (SFDT), Osebold method and Microtube Agglutination Test (MAT) respectively, from the blood serum samples., Results: 132 serum tested 56.06% samples of T. gondii, 40.9% and 3.03% of L. monocytogenes and defined the B.abortus antibodies were found to be seropositive terms. There were no statistically significant difference between seropositive T. gondii, L. monocytogenes and B.abortus antibodies among age groups (p>0.05)., Conclusion: In this study, for the first time in cattle in the region of Adana serological methods revealed the presence L. monocytogenes, toxoplasmosis and listeriosis were higher than brucellosis seropositivity. Moreover, the prevalence of these diseases in the same animal at the highest rate was determined for T. gondii and L. monocytogenes.

CD4 T cell memory generation is shaped by a number of factors, including the strength and duration of TCR signaling, as well as the priming environment, all of which can be modified by B cells. Studies using B cell-deficient mice indicate B cells play a critical role in generating effector and memory CD4 T cells; however, when and how B cells are acting to promote these responses has not yet been ascertained. In this study, we use anti-CD20 Ab depletion of B cells at different times following Listeria monocytogenes infection to show that B cells are necessary for the induction of optimal CD4 T cell memory, but not for the transition and maintenance of this population. Importantly, the prerequisite of B cells early postinfection is partially dependent on their expression of MHC class II. B cells are not only required during the priming phase, but also necessary for the initiation of robust secondary responses by memory CD4 T cells. Interestingly, the requirement during the recall response is independent of B cell Ag presentation. Overall, these studies demonstrate the temporally and functionally distinct roles for B cells in regulating CD4 T cell responses.

Background: To understand the increased susceptibility of preterm neonates to infection., Methods: A murine listeriosis model using immunohistochemistry, microarray technology, and real-time polymerase chain reaction (PCR)., Results: We report that recombinant serum amyloid A (SAA) administered prophylactically 18 h before intraperitoneal (i.p.) inoculation with Listeria monocytogenes conferred a dramatic survival benefit compared with administration of only vehicle in neonatal mice. Neonates that received the recombinant SAA protein had significantly fewer Listeria colony counts on plating of infected liver and showed significantly more activated macrophages, but SAA did not affect postnatal growth. Real-time PCR was used to confirm the microarray findings that gene expression levels for the SAA proteins 1 (Saa1) and 2 (Saa2), in addition to that for orosomucoid-2 (Orm2), were strikingly elevated in the adult compared with those in the neonate. Real-time PCR analysis showed that of the acute phase cytokines, tumor necrosis factor (TNF) gene expression increased exponentially with time in the infected adult, whereas neonates did not show similar increases., Conclusion: The increased susceptibility of neonatal mice to listeriosis is in part mediated by a deficiency in the acute phase response, specifically expression of SAA, and that prophylactic SAA protein before neonatal murine listeriosis results in more macrophage activation, lower Listeria counts, and greater survival.

CD8(+) T cells undergo rapid expansion during infection with intracellular pathogens, which is followed by swift and massive culling of primed CD8(+) T cells. The mechanisms that govern the massive contraction and maintenance of primed CD8(+) T cells are not clear. We show in this study that the transcription factor, FoxO3a, does not influence Ag presentation and the consequent expansion of CD8(+) T cell response during Listeria monocytogenes infection, but plays a key role in the maintenance of memory CD8(+) T cells. The effector function of primed CD8(+) T cells as revealed by cytokine secretion and CD107a degranulation was not influenced by inactivation of FoxO3a. Interestingly, FoxO3a-deficient CD8(+) T cells displayed reduced expression of proapoptotic molecules BIM and PUMA during the various phases of response, and underwent reduced apoptosis in comparison with wild-type cells. A higher number of memory precursor effector cells and memory subsets was detectable in FoxO3a-deficient mice compared with wild-type mice. Furthermore, FoxO3a-deficient memory CD8(+) T cells upon transfer into normal or RAG1-deficient mice displayed enhanced survival. These results suggest that FoxO3a acts in a cell-intrinsic manner to regulate the survival of primed CD8(+) T cells.

Serum profiling was used to distinguish mice infected with wild-type or mutant Listeria monocytogenes from noninfected control mice. Identifications of significant electrospray ionization mass spectrometry (ESI-MS) sera peak areas between Listeria-infected- and control mice were performed using t tests. ESI-MS cohort peak distributions differed from mice infected with wild-type or ∆actA Listeria versus control mice with p values of 0.00012 and 0.015, respectively. A "% wild-type Listeria peaks identified" assessment tool yielded values of 64 % for wild-type infection, 51 % for ∆actA infection, and 47 % for no infection. Receiver operator characteristic area discriminatory values were 0.97 (wild-type) and 0.82 (∆actA) versus controls. Predictive value measurements revealed overall test sensitivities of 88 % for wild-type infection and 63 % for ∆actA infection. These studies indicate that ESI-MS serum profiling holds promise for diagnosis of infection with intracellular pathogens such as Listeria and indicate that the technology could be useful in understanding the L. monocytogenes infection process.

In order to examine the genetic variation of clinical and food isolates of Listeria monocytogenes in Greece, a total of 61 L. monocytogenes non-duplicate isolates, recovered from clinical specimens (n=19) and food (n=42), were serotyped and genotyped using two different Random Amplification of Polymorphic DNA (RAPD) protocols and Multiple Locus Variable Number Tandem Repeat Analysis (MLVA). Serotype group 4b, 4d, 4e prevailed (39.4%), among both clinical and food isolates, followed by serotype group 1/2a, 3a (23.0%), which nevertheless was detected only among food isolates. The most discriminatory typing protocol was MLVA, which grouped four isolates into two pairs, while the remaining isolates produced unique fingerprints. Similar results were obtained when taking into account the combination of the two RAPD protocols (Simpson index 0.999); six isolates were grouped into three pairs, two of which were the pairs that were identified also by MLVA. Single use of each RAPD protocol resulted in inferior discrimination (Simpson index 0.978 and 0.997, respectively). In conclusion, the two molecular procedures, MLVA, and the combined RAPD protocols, produced similar results, showing that L. monocytogenes isolates from clinical and food specimens were highly heterogenous and that clustering was very uncommon.

Microbial-induced inflammation is important for eliciting humoral immunity. Genetic defects of NADPH oxidase 2-based proteins interrupt phagocyte superoxide generation and are the basis for the human immunodeficiency chronic granulomatous disease (CGD). Hyperinflammation is also a significant clinical manifestation of CGD. Herein, we evaluated humoral immunity in the phagocyte oxidase p47(phox)-deficient model of CGD and found that UV-inactivated Streptococcus pneumoniae and Listeria monocytogenes (Lm) elicited higher specific antibody (Ab) titers in p47(phox-/-) mice than wild-type (WT) mice. Both organisms elicited robust and distinct antigen-presenting cell maturation phenotypes, including IL-12 hypersecretion, and higher major histocompatibility complex II and costimulatory protein expression in Lm-stimulated p47(phox-/-) dendritic cells (DCs) relative to WT DCs. Furthermore, p47(phox-/-) DCs pulsed with Lm and adoptively transferred into naïve WT mice elicited Ab titers, whereas Lm-pulsed WT DCs did not elicit these titers. The observed robust p47(phox-/-) mouse humoral response was recapitulated with live Lm and sustained in vivo in p47(phox-/-) mice. Notably, anti-serum samples from p47(phox-/-) mice that survived secondary Lm infection were protective in WT and p47(phox-/-) mice that were rechallenged with secondary lethal Lm infection. These findings demonstrate a novel benefit of NADPH oxidase 2 deficiency (ie, dependent inflammation in antigen-presenting cell-mediated humoral immunity) and that anti-Lm Ab can be protective in an immunodeficient CGD host., (Published by Elsevier Inc.)

During the course of a microbial infection, different antigen presenting cells (APCs) are exposed and contribute to the ensuing immune response. CD8α(+) dendritic cells (DCs) are an important coordinator of early immune responses to the intracellular bacteria Listeria monocytogenes (Lm) and are crucial for CD8(+) T cell immunity. In this study, we examine the contribution of different primary APCs to inducing immune responses against Lm. We find that CD8α(+) DCs are the most susceptible to infection while plasmacytoid DCs are not infected. Moreover, CD8α(+) DCs are the only DC subset capable of priming an immune response to Lm in vitro and are also the only APC studied that do so when transferred into β2 microglobulin deficient mice which lack endogenous cross-presentation. Upon infection, CD11b(+) DCs primarily secrete low levels of TNFα while CD8α(+) DCs secrete IL-12 p70. Infected monocytes secrete high levels of TNFα and IL-12p70, cytokines associated with activated inflammatory macrophages. Furthermore, co-culture of infected CD8α(+) DCs and CD11b+ DCs with monocytes enhances production of IL-12 p70 and TNFα. However, the presence of monocytes in DC/T cell co-cultures attenuates T cell priming against Lm-derived antigens in vitro and in vivo. This suppressive activity of spleen-derived monocytes is mediated in part by both TNFα and inducible nitric oxide synthase (iNOS). Thus these monocytes enhance IL-12 production to Lm infection, but concurrently abrogate DC-mediated T cell priming.

The Listeria genus is distinguished into six species from which just one--Listeria monocytogenes is pathogenic for humans. The main route of acquisition of Listeria is through the ingestion of contaminated food products. An important element of the L. monocytogenes pathogenesis infection is affiliation with high-risk group of immunocompromised patients, infants or pregnant women, who infected by this microorganism can lead to miscarriage. Listeriosis can appear in the form of sepsis, infection of the nervous system or local abscesses. Another form of listeriosis is gastrointestinal tract infection--noticed in case of food poisoning outbreak.

Background: Susceptibility or resistance to infection with Listeria monocytogenes correlates with Selenium (Se) deficiency in response to infection., Results: Se-deficient mouse models of listeriosis were used to study the innate immune response during the course of L. monocytogenes infection. Blood samples from mouse models were used for Se status. The concentration of MDA, SOD, GPx and CAT in blood has revealed that lower Se level exist in Se-deficient mice. Intestine, mesenteric lymph node, liver, spleen and brain from each mouse were to study the bacterial burden in organs. The analysis of cell types of spleen from Se-deficient mice revealed that the ability of the host to elicit a rapid recruitment and activation of systemic innate immune response to infection was to a certain extent compromised under conditions of Se deficiency. The cytokine levels in the serum and cytokine expression levels in the livers from Se-deficient mice revealed that the innate immune response of Se-deficient mice was impaired throughout the course of infection. These results suggest that innate immune response is altered by Se deficiency after infection with L. monocytogenes., Conclusion: In conclusion, induced susceptibility of host resistance is associated with an impaired innate immune response following infection with L. monocytogenes in C57BL/6 Se-deficient mice.

The aim of this study was to determine seroprevalence of Neospora caninum in dairy cattle ranches with higher abortion rates and co-existence of Neospora caninum, Toxoplasma gondii, Brucella abortus, and Listeria monocytogenes antibodies. The blood samples were collected from dairy cows with history of abortion (n=234) as well as from pregnant cows that were (n=323) kept in the same ranches. N. caninum seroprevalence was 10.77% (60/557). The co-existence rate of N. caninum seropositivity with T. gondii, B. abortus and L. monocytogenes was 24.77% (138/557), 13.82% (77/557) and 42.85% (162/378), respectively. Only one animal had significant antibody titers for all analyzed infectious agents. The seroprevalence of N. caninum and T. gondii were significantly higher in pregnant cows than aborted cows (p<0.05 and p<0.001, respectively). As a result, the comprehensive data generated through this study can significantly contribute to understanding of serologic association of N. caninum with T. gondii, B. abortus and L. monocytogenes in pregnant and aborted dairy cows.

Cytohesin binder and regulator (Cybr) is known to regulate leukocyte adhesion and migration. However, its function in T-cells is poorly understood. Here, we investigated the role of Cybr in CD4(+) T-cell function and host immunity. Cybr inhibited p38 phosphorylation following CD4(+) T-cell stimulation. Since p38 regulates the expression of T-box expressed in T-cells (T-bet) but not GATA binding protein 3 (GATA-3) in T-cells, Cybr decreased the expression of T-bet and IFN-gamma in CD4(+) T-cells. Moreover, we found that host immunity against Listeria infection and IFN-gamma production in blood were significantly compromised in Cybr-overexpressing transgenic mice. In summary, our data suggest that Cybr represses the expression of T-bet and IFN-gamma via an inhibition of p38 in T-cells and consequently reduces host resistance to bacterial infection in mice.

1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and the vitamin D receptor (VDR) are important regulators of autoimmunity. The effect of the VDR on the ability of mice to fight a primary or secondary infection has not been determined. Young and old VDR knockout (KO) mice were able to clear both primary and secondary infections with Listeria monocytogenes. However, the kinetics of clearance was somewhat delayed in the absence of the VDR. Memory T cell development was not different in young VDR KO and wild-type (WT) mice; however, old VDR KO mice had significantly less memory T cells than their WT counterparts but still mounted an adequate immune response as determined by the complete clearance of L. monocytogenes. Although the primary and secondary immune responses were largely intact in the VDR KO mice, the old VDR KO mice had increased cytokines and antibody responses compared with the old WT mice. In particular, old VDR KO mice had elevated antigen non-specific antibodies; however, these magnified immune responses did not correspond to more effective Listeria clearance. The increased antibody and cytokine responses in the old VDR KO mice are consistent with the increased susceptibility of these mice to autoimmunity.

The food-borne pathogen Listeria monocytogenes is adapted to a diversity of environments, such as soil, food, body fluids, and the cytosol of eukaryotic cells. The transition between saprophytic and pathogenic life is mediated through complex regulatory pathways that modulate the expression of virulence factors. Here we examined the expression of inlJ, a recently identified gene encoding a protein of the LPXTG-internalin family and involved in pathogenesis. We show that inlJ expression is controlled neither by the major listerial regulator of virulence genes, PrfA, nor by AxyR, a putative AraC regulator encoded by a gene adjacent to inlJ and divergently transcribed. The InlJ protein is not produced by bacteria grown in vitro in brain heart infusion medium or replicating in the cytosol of tissue-cultured cells. In contrast, it is efficiently produced and localized at the surface of bacteria present in the liver and blood of infected animals. Strikingly, the expression of inlJ by a heterologous promoter in L. monocytogenes or L. innocua promotes bacterial adherence to human cells in vitro. Taken together, these results strongly suggest that InlJ acts as a novel L. monocytogenes sortase-anchored adhesin specifically expressed during infection in vivo.

Listeria monocytogenes may lead to intrauterine infections which can be treated if diagnosed promptly. However, there is not a rapid routine screening test with high specificity and sensitivity for the diagnosis of listeriosis during pregnancy. We investigated the presence of different L. monocytogenes O antibodies for diagnosis of listeriosis in 275 paired maternal-cord sera using the agglutination test, and aimed to evaluate the correlation between poor pregnancy outcomes, level of L. monocytogenes serotype O antibodies and risk factors for listeriosis. Maternal-cord bloods were collected from a total of 275 pregnant women (age range 16-38 years) between April-August 2002 from a State Hospital in Ankara. A total of 550 sera were tested against antigens with the O formulation of serotypes 1/2c, 3b, 4ab, 4c, 4d by tube agglutination method and titers > or = 1/320 were considered as positive. Sixtynine patients with the history of poor pregnancy outcomes were in group I, while 206 patients with no obstetric pathology in previous pregnancies were in group II. L. monocytogenes antibodies to one or more serotypes were detected in 21.5% (59/275) of the patients, the rate being 20.3% in group I and 21.8% in group II. No statistically significant difference was detected between the two study groups (p > 0.05), indicating that this test was not an appropriate marker for the diagnosis of listeriosis during pregnancy. The total rate of positive results in cord sera was 0.7% (2/275) and the positive two sera were from samples in group II. The follow-up of the newborns, including the two cord blood positive ones, revealed no fetomaternal infection. The most frequently detected serotypes were 4ab (40%) and 1/2c (37%). Risk factors such as non-specific febrile illness during pregnancy (p < 0.001), consumption of ready-made food (p = 0.008), consumption of raw milk and milk products (p < 0.001) were found to be related to the presence of > or = 1/320 titers of L. monocytogenes antibodies. The major limiting factor in this study was the inability to obtain second serum samples from the mothers and newborns following delivery, to confirm the diagnosis by seroconversion. These results emphasize the need for the development of rapid, simple and reliable tests, alternative to culture methods, for the early and proper diagnosis of Listeria infections during pregnancy.

The aryl hydrocarbon receptor (AhR) is part of a powerful signaling system that is triggered by xenobiotic agents such as polychlorinated hydrocarbons and polycyclic aromatic hydrocarbons. Although activation of the AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin or certain polycyclic aromatic hydrocarbons can lead to immunosuppression, there is also increasing evidence that the AhR regulates certain normal developmental processes. In this study, we asked whether the AhR plays a role in host resistance using murine listeriosis as an experimental system. Our data clearly demonstrate that AhR null C57BL/6J mice (AhR(-/-)) are more susceptible to listeriosis than AhR heterozygous (AhR(+/-)) littermates when inoculated i.v. with log-phase Listeria monocytogenes. AhR(-/-) mice exhibited greater numbers of CFU of L. monocytogenes in the spleen and liver, and greater histopathological changes in the liver than AhR(+/-) mice. Serum levels of IL-6, MCP-1, IFN-gamma, and TNF-alpha were comparable between L. monocytogenes-infected AhR(-/-) and AhR(+/-) mice. Increased levels of IL-12 and IL-10 were observed in L. monocytogenes-infected AhR(-/-) mice. No significant difference was found between AhR(+/-) and AhR(-/-) macrophages ex vivo with regard to their ability to ingest and inhibit intracellular growth of L. monocytogenes. Intracellular cytokine staining of CD4(+) and CD8(+) splenocytes for IFN-gamma and TNF-alpha revealed comparable T cell-mediated responses in AhR(-/-) and AhR(+/-) mice. Previously infected AhR(-/-) and AhR(+/-) mice both exhibited enhanced resistance to reinfection with L. monocytogenes. These data provide the first evidence that AhR is required for optimal resistance but is not essential for adaptive immune response to L. monocytogenes infection.

Purpose: This study focused on the effect of immuno-compromising conditions on the clinical presentation of severe listerial infection., Patients and Methods: Nine human listeriosis cases seen from 1991-2002 were reviewed. All adult patients, from whose blood, peritoneal fluid or cerebrospinal fluid (CSF) the L. monocytogenes was isolated, were included in this retrospective study., Results: Listeriosis presented as primary sepsis with positive blood cultures in 5 cases and meningitis with positive CSF cultures in 4 cases. All of these patients had at least one underlying disease, most commonly, hematologic malignancy, diabetes mellitus, amyloidosis and hepatic cirrhosis; 55.6% had received immunosuppressive or corticosteroid therapy within a week before the onset of listeriosis. The patients were adults with a mean age of 60 years. Fever, night sweats, chills and lethargy were the most common symptoms; high temperature (> 38 degrees C), tachycardia, meningeal signs and poor conditions in general were the most common findings on admission. The mortality rate was 33.3% and was strictly associated with the severity of the underlying disease. Mortality differences were significant between sepsis (20%) and meningitis (50%) patients., Conclusion: Listeriosis as an uncommon infection in our region and that immuno- suppressive therapy is an important pre-disposing factor of listeriosis. Sepsis and meningitis were more common in this group of patients and had the highest case-fatality rate for food-borne illnesses.

In Western developed countries, Listeria monocytogenesis not an uncommon pathogen in neonates. However, neonatal listeriosis has rarely been reported in Taiwan. We describe two cases collected from a single medical institute between 1990 and 2005. Case 1 was a male premature baby weighing 1558 g with a gestational age of 31 weeks whose mother had fever with chills 3 days prior to delivery. Generalized maculopapular rash was found after delivery and subtle seizure developed. Both blood and cerebrospinal fluid culture collected on the 1st day yielded L. monocytogenes. In addition, he had ventriculitis complicated with hydrocephalus. Neurologic development was normal over 1 year of follow-up after ventriculoperitoneal shunt operation. Case 2 was a 28-weeks' gestation male premature baby weighing 1180 g. Endotracheal intubation and ventilator support were provided after delivery due to respiratory distress. Blood culture yielded L. monocytogenes. Cerebrospinal fluid showed pleocytosis but the culture was negative. Brain ultrasonography showed ventriculitis. Sudden deterioration with cyanosis and bradycardia developed on the 8th day and he died on the same day. Neonatal listeriosis is uncommon in Taiwan, but has significant mortality and morbidity. Early diagnosis of perinatal infection relies on high index of suspicion in perinatal health care professionals.

A combined serological and PCR method for the detection of Listeria monocytogenes infection in symptomatic and asymptomatic ovine flocks was evaluated. Seventy-eight milk samples and 157 serum samples were analysed using a L. monocytogenes PCR detection kit and an anti-listeriolysin O IgG immunoassay kit. The combined use of these commercial kits allowed a rapid and effective detection of L. monocytogenes infection in both the early stage, before seroconversion, and in a later phase, even after antibiotic therapy.

Background: Efforts to reduce bacterial contamination in platelets (PLTs) have led to implementation of tests for bacterial detection before product release. Although relatively rare as a human pathogen, Listeria monocytogenes often causes serious illness and has a case-fatality rate of 20 percent., Case Report: PLTs from an asymptomatic 58- year-old Hispanic male with a long history of PLT donation were culture-positive for the presence of L. monocytogenes. The pulsed-field gel electrophoresis (PFGE) pattern of the isolate matched two other L. monocytogenes isolates in the CDC National PulseNet database. Public health investigation found no evidence that the other two isolates were epidemiologically related to the PLT donor, who remained asymptomatic., Conclusion: A cluster of listeriosis cases was detected by PFGE but the significance is unknown. Organisms of public health significance should be reported to health departments. Better surveillance and reporting are needed in the efforts to improve blood product safety.

The purpose of this study was to evaluate gene expression profiles in the liver and blood for prediction of infection severity from Listeria monocytogenes (LM). Mice were injected with medium broth (control) or a nonlethal or lethal dose of LM and sacrificed 6 h later. Gene expression changes were determined using Affymetrix MGU74Av2 GeneChips and confirmed by real-time polymerase chain reaction analysis. We identified discernable genes whose gene expression profiles can be used in pattern recognition to predict and classify samples in differently treated groups, with >or=90% accuracy in liver samples and 80% accuracy in blood at prediction; however, different genes were predictive in each tissue. Our results suggest that gene expression profiling in response to LM in mice may be able to distinguish samples in groups with varying severity of infection and provide information in finding molecular mechanisms and early biomarkers for subsequent conventional clinical endpoints.

Recent experimental observations have determined that long-chain n-3 polyunsaturated fatty acids suppress immune functions and are involved in the reduction of infectious disease resistance. BALB/c mice were fed for 4 weeks with one of four diets containing either olive oil (OO), fish oil (FO), hydrogenated coconut oil, or a low fat level. Interleukin-12p70 (IL-12p70), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) production in the sera of mice fed these diets and challenged with Listeria monocytogenes were determined by enzyme-linked immunosorbent assay. In addition, bacterial counts from spleens of mice were carried out at 24, 72, or 96 h of infection. Here, we quantified an initial diminution of production of both IL-12p70 and IFN-gamma, which appear to play an important role in the reduction of host resistance to L. monocytogenes infection. In addition, an efficient elimination of L. monocytogenes was observed in spleens of mice fed a diet containing OO at 96 h of infection, despite reductions in IL-12p70 and TNF-alpha production, suggesting an improvement of immune resistance. Overall, our results indicate that the initial reduction of both IL-12 and IFN-gamma production before L. monocytogenes infection represents the most relevant event that corroborates the impairment of immune resistance by n-3 polyunsaturated fatty acids during the different stages of infection. However, we speculate that the modulation of other cytokines must be also involved in this response, because the alteration of cytokine production in mice fed an FO diet in a late phase of L. monocytogenes infection was similar to that in mice fed OO, whereas the ability to eliminate this bacterium from the spleen was improved in the latter group.

Type I interferons (IFN-alpha/beta) were originally thought to be antiviral cytokines, but it has recently been reported that they also play an important role in potentiating innate and adaptive immune responses. Moreover, several studies have shown that the oral administration of type I IFN ameliorates various biologic activities. Here, we studied the ability of orally administered IFN-alpha to protect mice from systemic Listeria monocytogenes infection. Daily oral administration of purified natural IFN-alpha at a concentration of 1000 international units (IU)/20 microl reduced the bacterial burden in infected organs. We also examined the protective effect of IFN-alpha expressed in transgenic potato plants. A much lower concentration of IFN-alpha (20 IU/ 20 microl) in the plant extracts was almost as protective as much higher concentrations of purified natural IFN-alpha. Our observations indicate that transgenic cytokine-expressing plants can be used prophylactically as edible pharmaceuticals to enhance systemic defense responses in humans and animals.

Bacterial infections are major causes of human mortality. The activation of coagulation pathways leading to the deposition of insoluble fibrin frequently accompanies bacterial infection, and much attention has focused upon the pathological attributes of infection-stimulated fibrin deposition. Nevertheless, here we present conclusive evidence that infection-stimulated fibrin deposition can perform critical protective functions during bacterial infection. Specifically, we demonstrate that coagulation-impaired fibrin(ogen)-deficient mice, in comparison with genetically matched control mice, display increased mortality upon peritoneal infection with the gram-positive facultative intracellular bacterium Listeria monocytogenes. To distinguish effects of fibrinogen from those of fibrin, we treat wild-type mice with warfarin, an anticoagulant that suppresses fibrin formation without impacting fibrinogen levels. Warfarin treatment exacerbates listeriosis, suggesting that fibrin is the key mediator of protection. With regard to the underlying protective mechanisms, we demonstrate that fibrin(ogen) suppresses anemia, reduces hemorrhagic pathology, and limits bacterial growth during listeriosis. Despite confirming a prior report that fibrin(ogen) promotes the peritoneal clearance of the extracellular bacterium Staphylococcal aureus, we demonstrate that fibrin(ogen) plays little role in controlling peritoneal numbers of L. monocytogenes bacteria or the dissemination of L. monocytogenes bacteria from the peritoneal cavity. Rather, fibrin(ogen) primarily limits the growth of these intracellular bacteria within hepatic tissue. While the pathological potential of excessive infection-stimulated fibrin deposition is well appreciated, our findings reveal that fibrin can function protectively, via multiple mechanisms, during bacterial infection.

In this study, we demonstrated that Uncaria tomentosa extract (UTE) protects mice from a lethal dose of Listeria monocytogenes when administered prophylactically at 50, 100, 150 and 200 mg/kg for 7 days, with survival rates up to 35%. These doses also prevented the myelosuppression and the splenomegaly caused by a sublethal infection with L. monocytogenes, due to increased numbers of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow. Non-infected mice treated with 100 mg/kg UTE also presented higher numbers of CFU-GM in the bone marrow than the controls. Investigation of the production of colony-stimulating factors revealed increased colony-stimulating activity (CSA) in the serum of normal and infected mice pre-treated with UTE. Moreover, stimulation of myelopoiesis and CSA occurred in a dose-dependent manner, a plateaux being reached with the dose of 100 mg/kg. Further studies to investigate the levels of factors such as IL-1 and IL-6 were undertaken. We observed increases in the levels of IL-1 and IL-6 in mice infected with L. monocytogenes and treated with 100 mg/kg of UTE. White blood cells (WBC) and differential counting were also performed, and our results demonstrated no significant changes in these data, when infected mice were pre-treated with 100 mg/kg of UTE. All together, our results suggest that UTE indirectly modulates immune activity and probably disengages Listeria-induced supression of these responses by inducing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (CSFs, IL-1 and IL-6).

The isolation of pathogenic Listeria spp. in bacteriological samples, and anti-phosphatidylinositol-specific phospholipase C (anti-PIPLC) antibodies in sera of buffaloes were studied. Isolation of the pathogen was attempted from the samples by selective enrichment in University of Vermont Medium and plating onto Dominguez-Rodriguez isolation agar. Pathogenicity of the isolates was tested by Christie, Atkins, Munch Petersen test and mice incoulation test. Listeria spp. and L. monocytogenes were isolated from 8.8 and 2.4%, and 4.8 and 1.6% of 125 each meat and blood samples, respectively. Out of the 125 samples each of feacal, nasal and vaginal swabs from buffaloes 8 and 4%, 13.6 and 2.4%, and 6.4 and 2.4% were positive for Listeria spp. and L. monocytogenes, respectively. L. ivanovii was confirmed from 0.8% vaginal sample. A total of 125 serum samples were tested by phosphatidylinositol-specific phospholipase C (PIPLC) based indirect ELISA of which 4.0% turned out to be seropositive.

Recombinant listeriolysin O and internalin A were used as antigens in an enzyme-linked immunosorbent assay (ELISA) for the specific detection of anti-Listeria monocytogenes antibodies in cattle. The results showed sensitivities and specificities of 82 and 92%, respectively, for the listeriolysin O ELISA, and 100 and 90%, respectively, for the internalin A ELISA, respectively. The test may be useful for the confirmation of listeria-related abortions and mastitis but does not seem to be indicated for use in the diagnosis of listeria-related encephalitis in cattle. A representative sample of 1,652 serum samples from the healthy dairy cattle population in Switzerland was tested by both ELISAs. The results showed that 11% of the healthy dairy cows in Switzerland simultaneously presented antibodies toward listeriolysin O and internalin A, and 48% of the farms had one or several animals simultaneously positive by assays with both antigens. Multivariable analysis at the farm level confirmed that feeding of silage represents a significant risk factor for a positive listeria serology. Detailed analysis identified corn silage but not grass silage as the major factor in this association. Cattle breed and hygiene on the farm were also identified as significant factors associated with the serological status of farms. In conclusion, the results of the study show that internalin A is a promising new antigen for use in listeria serology and that specific anti-L. monocytogenes antibodies are found in a significant proportion of healthy dairy cows in Switzerland.

Most bacteria that enter the bloodstream are taken up and eliminated within the liver. The specific mechanisms that underlie the role of the liver in the resolution of systemic bacterial infections remain to be determined. The vast majority of studies undertaken to date have focused on the function of resident tissue macrophages (Kupffer cells) that line the liver sinusoids. Indeed, it is often reported that Kupffer cells ingest and kill the bulk of organisms taken up by the liver. Recent studies indicate, however, that phagocytosis by Kupffer cells is not the principal mechanism by which organisms are eliminated. Rather, elimination depends on the complex interaction of Kupffer cells and bactericidal neutrophils that immigrate rapidly to the liver in response to infection. We discuss the critical role of neutrophil-Kupffer cell interaction in innate host defenses and, conceivably, the development and expression of adaptive immunity in the liver.

The intestinal mucosal CD8 T cell response to infection with Listeria monocytogenes was measured using MHC class I tetramers and was compared with the response in peripheral blood, secondary lymphoid tissue, and liver. To assess the vaccination potential of Listeria and to analyze responses in C57BL/6 mouse strains, a recombinant Listeria expressing OVA (rLM-ova) was generated. The response peaked at 9 days postinfection with a much larger fraction of the intestinal mucosa and liver CD8 T cell pool OVA specific, as compared with the spleen. However, these differences were not linked to bacterial titers in each site. The higher responses in lamina propria and liver resulted in a larger CD8 memory population in these tissues. Furthermore, the level of memory induced was dependent on infectious dose and inversely correlated with the magnitude of the recall response after oral challenge. Recall responses in the tissues were most robust in the lamina propria and liver, and reactivated Ag-specific T cells produced IFN-gamma. Infection of CD40- or MHC class II-deficient mice induced poor CD8 T cell responses in the intestinal mucosa, but only partially reduced responses in the spleen and liver. Overall, the results point to novel pathways of tissue-specific regulation of primary and memory antimicrobial CD8 T cell responses.

The relationships between Listeria monocytogenes (LM) pathogenesis, based on bacterial load, and serum levels of IL-6, IFNgamma, and corticosterone (CORT) were quantified. Serum IFNgamma levels increased along with the LM burden; however, with LM burdens > or =3 x 10(6) CFU per spleen, the serum IFNgamma level decreased along with a decrease in splenic weight. Serum IL-6 levels exponentially increased with increases of LM, and the CORT level positively correlated with the increase in IL-6 and LM. The serum level of IFNgamma appeared to be a good biomarker of the host's ability to combat the infection only when the LM burden did not exceed a critical level (>3 x 10(6) CFU per spleen). Interestingly, the LM load at which the IFNgamma level began to decline was near the dose at which the IL-6 concentration exponentially increased, suggesting a transition point shift from stress (assessed as CORT level) being immunoenhancing to becoming immunosuppressive. The IL-6:IFNgamma ratio may be a good indicator of disease severity and/or the ability to cope with an infection., (Copyright 2001 Academic Press.)

In mice, individual dietary omega-3 polyunsaturated fatty acids n-3 (PUFA) were found to be sufficient to effect the changes in circulating interleukin (IL)-12 and interferon (IFN)-gamma levels that were previously seen in fish oil-fed mice. Weanling female C3H mice were fed one of five experimental diets. All five diets met all known nutritional requirements for mice and differed only in the fat source. After 4 weeks, mice were challenged with live Listeria monocytogenes or sterile PBS. Twenty-four hours after infection, n-3 PUFA-fed mice had significantly lower circulating IL-12 p70 and IFN-gamma than mice fed the control diet (P<.01). In addition, splenic cytokine mRNA for IL-12 p40, tumor necrosis factor-alpha, and IL-1beta were lower in infected mice fed n-3 PUFA-containing diets than in mice fed the olive oil ethyl esters control diet. The reduction of IL-12 and IFN-gamma production by n-3 PUFA may have important implications for host infectious disease resistance.

In this study, the effect of traditional Japanese (Chinese) medicine, Bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to, HOT), on the restraint stress treatment (RST)-induced susceptibility against Listeria monocytogenes (L. monocytogenes) was examined. When RST was performed every day for 10 h from the day of infection, the bacterial numbers were increased at 3 and 5 days after the infection. Oral pretreatment with HOT for 7 days prevented such increases. Pretreatment with HOT prevented the suppression of antigen-specific IFN-gamma production by RST. HOT also prevented suppression of macrophage accumulation, including MHC-class II positives, in the peritoneal cavity and their bactericidal activity by RST. HOT suppressed the serum corticosterone level elevated by RST in infected mice. Taken together, the suppression of corticosterone using HOT participates in the prevention of suppressions of the bactericidal activity of macrophages, migration of macrophages and antigen-specific IFN-gamma production of Th1 cells by RST. Our findings suggest that HOT is a useful drug for patients suffering from stress disease to reduce the susceptibility to bacterial infection.