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Host Immunity (host + immunity)

Distribution by Scientific Domains

Medical Sciences	66%
Life Sciences	20%
Chemistry	12%

Selected Abstracts

Host immunity modulates transcriptional changes in a multigene family (yir) of rodent malaria

MOLECULAR MICROBIOLOGY, Issue 3 2005
Deirdre A. Cunningham
Summary Variant antigens, encoded by multigene families, and expressed at the surface of erythrocytes infected with the human malaria parasite Plasmodium falciparum and the simian parasite Plasmodium knowlesi, are important in evasion of host immunity. The vir multigene family, encoding a very large number of variant antigens, has been identified in the human parasite Plasmodium vivax and homologues (yir) of this family exist in the rodent parasite Plasmodium yoelii. These genes are part of a superfamily (pir) which are found in Plasmodium species infecting rodents, monkeys and humans (P. yoelii, P. berghei, P. chabaudi, P. knowlesi and P. vivax). Here, we show that YIR proteins are expressed on the surface of erythrocytes infected with late-stage asexual parasites, and that host immunity modulates transcription of yir genes. The surface location and expression pattern of YIR is consistent with a role in antigenic variation. This provides a unique opportunity to study the regulation and expression of the pir superfamily, and its role in both protective immunity and antigenic variation, in an easily accessible animal model system. [source]

Host immunity affects survival in myelodysplastic syndromes: Independent prognostic value of the absolute lymphocyte count,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2010
Nisha L. Jacobs
The prognostic significance of the peripheral blood absolute lymphocyte count (ALC) has been carefully examined in lymphoid malignancies, but the importance of the baseline ALC in chronic myeloid neoplasms is less clear. In a recent analysis of myelodysplastic syndromes (MDS) associated with deletion of chromosome 5q, we observed that an ALC < 1.2× 109 cells/L at diagnosis is independently associated with poorer survival. Clinicopathological data from 503 patients with non-del(5q) MDS evaluated at Mayo Clinic between 1996 and 2007 were reviewed to determine the prognostic impact of ALC at diagnosis in non-del(5q) MDS. Patients with MDS and an ALC at diagnosis ,1.2× 109 (N = 248) experienced a superior overall survival (OS) compared with patients with an ALC < 1.2× 109/L (N = 255, median OS of 26.6 months versus 18.5 months, P < 0.001, respectively). ALC at diagnosis was an independent predictor for OS when compared with the International Prognostic Scoring System and the WHO-based Prognostic Scoring System. This study suggests that ALC at diagnosis is a prognostic factor for OS in MDS, and argues in favor of further studies to assess the role of host immunity in MDS clinical outcomes. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source]

The immune response to Naegleria fowleri amebae and pathogenesis of infection

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2007
Francine Marciano-Cabral
Abstract The genus Naegleria is comprised of a group of free-living ameboflagellates found in diverse habitats worldwide. Over 30 species have been isolated from soil and water but only Naegleria fowleri (N. fowleri) has been associated with human disease. Naegleria fowleri causes primary amebic meningoencephalitis (PAM), a fatal disease of the central nervous system. The pathogenesis of PAM and the role of host immunity to N. fowleri are poorly understood. Strategies for combating infection are limited because disease progression is rapid and N. fowleri has developed strategies to evade the immune system. The medical significance of these free-living ameboflagellates should not be underestimated, not only because they are agents of human disease, but also because they can serve as reservoirs of pathogenic bacteria. [source]

The role of genome diversity and immune evasion in persistent infection with Helicobacter pylori

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2005
Cara L. Cooke
Abstract Helicobacter pylori is an important human pathogen that chronically colonizes the stomach of half the world's population. Infection typically occurs in childhood and persists for decades, if not for the lifetime of the host. How is bacterial persistence possible despite a vigorous innate and adaptive immune response? Here we describe the complex role of bacterial diversity and specific mechanisms to avoid or subvert host immunity in bacterial persistence. We suggest that H. pylori finely modulates the extent to which it interacts with the host in order to promote chronic infection, and that it uses diverse mechanisms to do so. [source]

Mechanisms of pathogenesis and the evolution of parasite virulence

JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 2 2008
S. A. FRANK
Abstract When studying how much a parasite harms its host, evolutionary biologists turn to the evolutionary theory of virulence. That theory has been successful in predicting how parasite virulence evolves in response to changes in epidemiological conditions of parasite transmission or to perturbations induced by drug treatments. The evolutionary theory of virulence is, however, nearly silent about the expected differences in virulence between different species of parasite. Why, for example, is anthrax so virulent, whereas closely related bacterial species cause little harm? The evolutionary theory might address such comparisons by analysing differences in tradeoffs between parasite fitness components: transmission as a measure of parasite fecundity, clearance as a measure of parasite lifespan and virulence as another measure that delimits parasite survival within a host. However, even crude quantitative estimates of such tradeoffs remain beyond reach in all but the most controlled of experimental conditions. Here, we argue that the great recent advances in the molecular study of pathogenesis provide a way forward. In light of those mechanistic studies, we analyse the relative sensitivity of tradeoffs between components of parasite fitness. We argue that pathogenic mechanisms that manipulate host immunity or escape from host defences have particularly high sensitivity to parasite fitness and thus dominate as causes of parasite virulence. The high sensitivity of immunomodulation and immune escape arise because those mechanisms affect parasite survival within the host, the most sensitive of fitness components. In our view, relating the sensitivity of pathogenic mechanisms to fitness components will provide a way to build a much richer and more general theory of parasite virulence. [source]

Hepatitis B reactivation in patients receiving cytotoxic chemotherapy: Diagnosis and management

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2010
John S Lubel
Abstract Nearly one third of the world's population have been infected with hepatitis B and the virus is endemic in many Asian countries. With increasing life expectancy and the expected global increase in cancer, chemotherapy induced reactivation of hepatitis B is likely to become an increasing problem. Patients with significant levels of hepatitis B virus (HBV) DNA in serum prior to chemotherapy and patients receiving intensive chemotherapy for hematological malignancies appear particularly at risk. Most patients who suffer reactivation of hepatitis B are positive for hepatitis B surface antigen (HBsAg) prior to chemotherapy and are therefore easily identifiable by routine screening. In addition, the very large population of patients who have been exposed to the virus and have apparently cleared the virus as assessed by serological testing (HBsAg negative/hepatitis B core antibody [HBcAb] positive) may also be at risk of reactivation. These patients should be monitored and in some cases receive prophylaxis during chemotherapy. Published experience with antiviral prophylaxis has largely been limited to the nucleoside analogue, lamivudine. The commencement of antiviral prophylaxis prior to chemotherapy and its continuation until restitution of normal host immunity is the cornerstone to effective prevention of hepatitis B reactivation. This review summarizes the important issues related to HBV reactivation and suggests an algorithm for managing these patients in the clinical setting. [source]

DOES THE CYTOSKELETON OF INTESTINAL EPITHHELIAL CELLS FUNCTION AS A CELLULAR ALARM TO IDENTIFY THE E. COLI INFECTION

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2001
Zhe Li
Intestinal epithelial cells play an important role in regulating host immunity in response to intestinal infection. Pathogenic bacteria (EPEC and EHEC) cause profound cytoskeletal rearrangement in intestinal epithelial cells during attachment or invasion. Rearrangement of cytoskeletal proteins could be a signal to up-regulate host defence response. Aims, To determine the role of actin cytoskeleton and microtubles in IL-8 mRNA response to E. coli infection. Methods, T84 cell monolayers in 6-well plates were infected with HB101, EPEC and EHEC (105 CFU/well) and compared with uninfected control at 3, 6 and 12 h post infection. Control and infected monolayers were treated with nocodazole (Noc, microtubule disrupter, 30 mm), taxol (Tax, microtubule stabiliser, 10 mm), cytochalasin D (CytoD, actin depolymeriser, 100 nm) and Jasplakinolide (Jasp, actin polymeriser, stabilise actin filaments, 1 mm) and studied 6 h post infection. IL-8 gene expression was measured by semiquantitative RT,PCR in control and uninfected monolayers with and without drug treatment and IL8 protein secretion by ELISA. The morphology of F-actin and ,-tubulin was examined by FITC-phaloidin staining (FAS), immunohistochemistry and confocal microscopy. Results, IL-8 mRNA and IL-8 were increased by infection with all bacterial strains at 3 and 6 h but both IL-8 mRNA and IL-8 in EHEC and EPEC infection were decreased compared with control and HB101 at 12 h. Disruption of microfilaments by Noc increased IL-8 (2.7 fold) while preservation of microfilaments by Tax inhibited IL8 response (0.5 fold) to HB101 infection only. CytoD decreased (0.1,0.5 fold) IL8 expression at all time points in all infections while stabilising actin by Jasp markedly increased the IL8 response (2,6 fold) in control, HB101, EHEC and EPEC at 3 and 6 h. CytoD inhibited Noc-induced IL8 gene expression. Confocal microscopy demonstrated that CytoD and Noc caused major morphological damage to the actin and ,-tubulin by 6 h. Similar changes were also observed in EPEC and EHEC infection at 12 h but not HB101. Jasp preserved actin stress filaments in both EPEC and EHEC. Conclusions, Disruption of microtubules and exogenous rearrangement of actin by pathogenic organism may be primary stimuli to up-regulate proinflammatory cytokine gene expression. Preservation of actin filaments is required for this response and may be necessary for signal transduction to the nucleus. [source]

Host immunity modulates transcriptional changes in a multigene family (yir) of rodent malaria

Complement and fungal pathogens: an update

MYCOSES, Issue 6 2008
Cornelia Speth
Summary Fungal infections are a serious complication in immunocompromised patients such as human immunodeficiency virus-infected individuals, patients with organ transplantations or with haematological neoplasia. The lethality of opportunistic fungal infection is high despite a growing arsenal of antimycotic drugs, implying the urgent need for supportive immunological therapies to strengthen the current inefficient antimicrobial defences of the immunocompromised host. Therefore, increasing effort has been directed to investigating the interplay between fungi and the host immunity and thus to find starting points for additional therapeutic approaches. In this article, we review the actual state of the art concerning the role of complement in the pathogenesis of fungal infections. Important aspects include the activation of the complement system by the fungal pathogen, the efficiency of the complement-associated antimicrobial functions and the arsenal of immune evasion strategies applied by the fungi. The twin functions of complement as an interactive player of the innate immunity and at the same time as a modulator of the adaptive immunity make this defence weapon a particularly interesting therapeutic candidate to mobilise a more effective immune response and to strengthen in one fell swoop a broad spectrum of different immune reactions. However, we also mention the ,Yin-Yang' nature of the complement system in fungal infections, as growing evidence assigns to complement a contributory part in the pathogenesis of fungus-induced allergic manifestations. [source]

The immunology of susceptibility and resistance to scabies

PARASITE IMMUNOLOGY, Issue 8 2010
S. F. WALTON
Summary The transmission of scabies occurs with the burrowing of Sarcoptes scabiei var. hominis mites into the skin. Infestation invariably leads to the development of localized cutaneous inflammation, pruritis and skin lesions. Classical transmission studies document an initial increase in S. scabiei numbers subsequent to primary infestation with a gradual reduction as host immunity develops. However, certain individuals fail to control infection and develop severe crusting of the skin, accompanied with extremely high mite burdens, elevated antibody levels and eosinophilia. These individuals have the nonhealing form of the human disease known as crusted scabies. The genetic predisposition for susceptibility or resistance to S. scabiei infection in humans is hypothesized to correlate with the dominance of an IgE-driven Th2 response in severe disease or an interferon-,-dominated Th1 response that promotes parasite control. However, recent data reveals complexities in cytokine regulation in the skin and the mechanisms of acquired resistance and immune escape. In this review, we consider the recent immunological and biomolecular advances in understanding the human host immune response to S. scabiei infestations in the context of earlier studies and attempt to reconcile apparent differences and emphasize those aspects of the Th1/Th2 model that are supported or refined. [source]

Manipulating host immunity to improve nematode parasite control ,Quo vadit

PARASITE IMMUNOLOGY, Issue 2 2008
A. R. SYKES
First page of article [source]

Host immunity affects survival in myelodysplastic syndromes: Independent prognostic value of the absolute lymphocyte count,

Absolute lymphocyte count at the time of first relapse predicts survival in patients with diffuse large B-cell lymphoma

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2009
Luis F. Porrata
Peripheral blood absolute lymphocyte count (ALC) is a survival prognostic factor in hematological malignancies. No reports have addressed whether ALC at the time of first relapse (ALC-R) predicts survival. Thus, we assessed the prognostic significance of ALC-R in diffuse large B-cell lymphoma (DLBCL). Patients were required to have been diagnosed with first relapsed DLBCL, have ALC-R values, and to be followed at Mayo Clinic, Rochester. From Feb 1987 until March 2006, 97 first relapsed DLBCL patients qualified for the study. The overall survival (OS) and progression-free survival (PFS) were measured from the time of first relapse. The value of ALC- R , 1.0 × 109/L was used for the analysis. Both groups (ALC-R , 1 or < 1 × 109/L) were balanced for the international prognostic index at relapse (IPI-R) (P = 0.3), and for autologous stem cell transplantation (P = 0.4). Superior OS and PFS were observed with an ALC-R , 1.0 × 109/L (N = 60) versus ALC-R < 1.0 × 109/L (N = 37) [median OS: 28.7 months, 5 years OS rates of 39% versus median OS: 10.2 months, 5 years OS rates of 14%, P < 0.002; and median PFS: 14.8 months, 5 years PFS rates of 21% versus median PFS: 6.5 months, 5 years PFS rates of 8%, P < 0.004, respectively]. ALC-R was an independent prognostic factor for OS [RR = 0.4, P < 0.01] and PFS [RR = 0.5, P < 0.005]. ALC-R predicts survival suggesting that host immunity is an important variable predicting survival in first relapsed DLBCL. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source]

Opportunistic infections and other risks with newer multiple sclerosis therapies,

ANNALS OF NEUROLOGY, Issue 4 2009
Joseph R. Berger MD
The introduction of newer therapies for the treatment of multiple sclerosis has generated considerable optimism. That optimism has been tempered by the potential risks of these therapies, such as the risk for progressive multifocal leukoencephalopathy. A review of the possible causes of reactivation of JC virus in this population has illustrated the need to better understand the untoward effects of monoclonal antibody therapies and other immunomodulatory therapies currently being contemplated for use in multiple sclerosis. These drugs alter the immune response at different sites, and most, if not all, affect more than one aspect of host immunity. Drawing from existing experience with the use of these immunomodulatory therapies in other conditions and that available from the limited experience with multiple sclerosis, we review their potential untoward effects. The latter include a predisposition to opportunistic and community-acquired infections, an altered response to vaccination, the development of cancers, and the appearance of autoimmune diseases. The identification of progressive multifocal leukoencephalopathy as a risk of therapy is relatively straightforward in light of its rarity and high morbidity and mortality, but a relatively slight increased risk for more common and less disabling disorders may be overlooked. Determining the actual risk frequency for many of these complications will likely require careful postmarketing surveillance. Ann Neurol 2009;65:367,377 [source]

Inhibition of bacterial translocation by chronic ethanol consumption in the rat,

APMIS, Issue 12 2001
VALERIA BENDER BRAULIO
Chronic ethanol ingestion has been associated with small intestine morphological changes, disrupted host mucosal defenses and bacterial overgrowth. Since bacterial translocation (BT) may result from such alterations, we have investigated the potential effect of chronic ethanol consumption on BT. For this purpose, male Wistar rats were fed a liquid diet containing 5% v/v ethanol for 4 weeks (EG, n=16), and a pair-fed group received equal daily amounts of calories in a similar diet without ethanol (PFG, n=16). On experimental day 29, distal ileum ligature and small intestine inoculation of a tetracycline-resistant E. coli strain (Tc®E. coli R6) followed by duodenal ligature was performed. After 1 or 5 h post inoculation, mesenteric lymph nodes, liver, spleen and kidney were excised. Unexpectedly, rats of the EG presented markedly less BT to the mesenteric lymph nodes (p<0.001) and to the other organs examined compared to rats of the PFG. This BT inhibition was observed at 1 and 5 h after bacterial inoculation, and may be attributed exclusively to chronic ethanol ingestion. Since alcoholism is well known to decrease host immunity, these results suggest that other factors, independent of the immune function, may be involved in the BT inhibition observed in this study. [source]

Bracovirus gene products are highly divergent from insect proteins

ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 4 2008
Annie Bézier
Abstract Recently, several polydnavirus (PDV) genomes have been completely sequenced. The dsDNA circles enclosed in virus particles and injected by wasps into caterpillars appear to mainly encode virulence factors potentially involved in altering host immunity and/or development, thereby allowing the survival of the parasitoid larvae within the host tissues. Parasitoid wasps generally inject virulence factors produced in the venom gland. As PDV genomes are inherited vertically by wasps through a proviral form, wasp virulence genes may have been transferred to this chromosomal form, leading to their incorporation into virus particles. Indeed, many gene products from Cotesia congregata bracovirus (CcBV), such as PTPs, I,B-like, and cystatins, contain protein domains conserved in metazoans. Surprisingly however, CcBV virulence gene products are not more closely related to insect proteins than to human proteins. To determine whether the distance between CcBV and insect proteins is a specific feature of BV proteins or simply reflects a general high divergence of parasitoid wasp products, which might be due to parasitic lifestyle, we have analyzed the sequences of wasp genes obtained from a cDNA library. Wasp sequences having a high similarity with Apis mellifera genes involved in a variety of biological functions could be identified indicating that the high level of divergence observed for BV products is a hallmark of these viral proteins. We discuss how this divergence might be explained in the context of the current hypotheses on the origin and evolution of wasp-bracovirus associations. Arch. Insect Biochem. Physiol. 67:172,187, 2008. © 2008 Wiley-Liss, Inc. [source]

Structure of NS1A effector domain from the influenza A/Udorn/72 virus

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2009
Shuangluo Xia
The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented. [source]

Crystallization and preliminary crystallographic analysis of the ADP-ribosyltransferase HopU1

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 8 2010
Yan Lin
Several Gram-negative pathogens of plants and animals and some eukaryotic associated bacteria use type III protein-secretion systems (T3SSs) to deliver bacterial virulence-associated `effector' proteins directly into host cells. HopU1 is a type III effector protein from the plant pathogen Pseudomonas syringae, which causes plant bacterial speck disease. HopU1 quells host immunity through ADP-ribosylation of GRP7 as a substrate. HopU1 has been reported as the first ADP-ribosyltransferase virulence protein to be identified in a plant pathogen. Although several structures of ADP-ribosyltransferases have been determined to date, no structure of an ADP-ribosyltransferase from a plant pathogen has been determined. Here, the protein expression, purification, crystallization and preliminary crystallographic analysis of HopU1 are reported. Diffracting crystals were grown by hanging-drop vapour diffusion using polyethylene glycol 10,000 as a precipitant. Native and SAD data sets were collected using native and selenomethionine-derivative HopU1 crystals. The diffraction pattern of the crystal extended to 2.7,Å resolution using synchrotron radiation. The crystals belonged to space group P43, with unit-cell parameters a = 92.6, b = 92.6, c = 101.6,Å. [source]

Perspectives on cancer immuno-epidemiology

CANCER SCIENCE, Issue 12 2004
Kei Nakachi
Estimating human cancer risk based on host-environment interaction is one task of epidemiology, and it has provided indispensable knowledge for prevention of cancer. The recent development of gene-engineered mice has also provided solid evidence about the relationship between cancer development and immunity. The aim of this review is to discuss the possible contribution of epidemiology to understanding the role of immunity in host defense against cancer, and also to assess the involvement of inflammation in the occurrence of selected cancers. Here we look at the concepts of cancer immunosurveillance and infection-inflammation-cancer, and include a brief introduction to recent studies in humans and experimental animal models. It has been postulated for many years that the immune system has the ability to recognize and eliminate nascent transformed cells in the body (so-called cancer immunosurveillance hypothesis), and this idea has recently obtained strong support from animal experiments. In humans, follow-up studies among immunosuppressed transplant recipients revealed a remarkably increased risk of not only selected malignancies, but also cancers with no known viral etiology. On the other hand, a prospective cohort study among the general population revealed that individuals with low natural cytotoxic activity of peripheral blood lymphocytes had an increased risk of cancer development. More studies are warranted to allow the construction of a model for the interaction between host immunity, aging, and the environment. The host immune system is also involved in inflammatory responses to pathogen infection: insufficient immune function of the host, or repeated infection, may result in persistent inflammation, where growth/ survival factors continuously act on initiated cells. The combined use of biomarkers will be necessary to define low-grade persistent inflammation in future cohort studies; and, in addition to these phenotype marker-based cohort studies, one plausible future direction will be a genomic approach that can be undertaken within cohort studies, looking at the genetic background underlying individual variations in phenotype markers. [source]

Induction of type I interferons by bacteria

CELLULAR MICROBIOLOGY, Issue 7 2010
Kathryn M. Monroe
Summary Type I interferons (IFNs) are secreted cytokines that orchestrate diverse immune responses to infection. Although typically considered to be most important in the response to viruses, type I IFNs are also induced by most, if not all, bacterial pathogens. Although diverse mechanisms have been described, bacterial induction of type I IFNs occurs upon stimulation of two main pathways: (i) Toll-like receptor (TLR) recognition of bacterial molecules such as lipopolysaccharide (LPS); (ii) TLR-independent recognition of molecules delivered to the host cell cytosol. Cytosolic responses can be activated by two general mechanisms. First, viable bacteria can secrete stimulatory ligands into the cytosol via specialized bacterial secretion systems. Second, ligands can be released from bacteria that lyse or are degraded. The bacterial ligands that induce the cytosolic pathways remain uncertain in many cases, but appear to include various nucleic acids. In this review, we discuss recent advances in our understanding of how bacteria induce type I interferons and the roles type I IFNs play in host immunity. [source]

Elicitation and suppression of microbe-associated molecular pattern-triggered immunity in plant,microbe interactions

CELLULAR MICROBIOLOGY, Issue 6 2007
Ping He
Summary Recent studies have uncovered fascinating molecular mechanisms underlying plant,microbe interactions that coevolved dynamically. As in animals, the primary plant innate immunity is immediately triggered by the detection of common pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs). Different MAMPs are often perceived by distinct cell-surface pattern-recognition receptors (PRRs) and activate convergent intracellular signalling pathways in plant cells for broad-spectrum immunity. Successful pathogens, however, have evolved multiple virulence factors to suppress MAMP-triggered immunity. Specifically, diverse pathogenic bacteria have employed the type III secretion system to deliver a repertoire of virulence effector proteins to interfere with host immunity and promote pathogenesis. Plants challenged by pathogens have evolved the secondary plant innate immunity. In particular, some plants possess the specific intracellular disease resistance (R) proteins to effectively counteract virulence effectors of pathogens for effector-triggered immunity. This potent but cultivar-specific effector-triggered immunity occurs rapidly with localized programmed cell death/hypersensitive response to limit pathogen proliferation and disease development. Remarkably, bacteria have further acquired virulence effectors to block effector-triggered immunity. This review covers the latest findings in the dynamics of MAMP-triggered immunity and its interception by virulence factors of pathogenic bacteria. [source]

The ,microflora hypothesis' of allergic diseases

CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2005
M. C. Noverr
Summary Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in ,industrialized' countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this ,microflora hypothesis' includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a ,balanced' microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy. [source]

Selective effects of Lactobacillus casei Shirota on T cell activation, natural killer cell activity and cytokine production

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010
H. Dong
Summary Modulation of host immunity is an important potential mechanism by which probiotics confer health benefits. This study was designed to investigate the effects of a probiotic strain, Lactobacillus casei Shirota (LcS), on immune function using human peripheral blood mononuclear cells (PBMC) in vitro. In addition, the role of monocytes in LcS-induced immunity was also explored. LcS promoted natural killer (NK) cell activity and preferentially induced expression of CD69 and CD25 on CD8+ and CD56+ subsets in the absence of any other stimulus. LcS also induced production of interleukin (IL)-1,, IL-6, tumour necrosis factor (TNF)-,, IL-12 and IL-10 in the absence of lipopolysaccharide (LPS). In the presence of LPS, LcS enhanced IL-1, production but inhibited LPS-induced IL-10 and IL-6 production, and had no further effect on TNF-, and IL-12 production. Monocyte depletion reduced significantly the impact of LcS on lymphocyte activation, cytokine production and natural killer (NK) cell activity. In conclusion, LcS activated cytotoxic lymphocytes preferentially in both the innate and specific immune systems, which suggests that LcS could potentiate the destruction of infected cells in the body. LcS also induced both proinflammatory and anti-inflammatory cytokine production in the absence of LPS, but in some cases inhibited LPS-induced cytokine production. Monocytes play an important role in LcS-induced immunological responses. [source]

Differential immunomodulatory properties of Bifidobacterium logum strains: relevance to probiotic selection and clinical applications

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007
M. Medina
Summary Modulation of host immunity is one of the proposed benefits of the consumption of probiotics. Nonetheless, comparative studies on the immunological properties that support the selection of strains of the same species for specific health benefits are limited. In this study, the ability of different strains of Bifidobacterium longum to induce cytokine production by peripheral blood mononuclear cells (PBMCs) has been evaluated. Live cells of all B. longum strains greatly stimulated regulatory cytokine interleukin (IL)-10 and proinflammatory cytokine tumour necrosis factor (TNF)-, production. Strains of the same species also induced specific cytokine patterns, suggesting that they could drive immune responses in different directions. The probiotic strain B. longum W11 stimulated strongly the production of T helper 1 (Th1) cytokines while B. longum NCIMB 8809 and BIF53 induced low levels of Th1 cytokines and high levels of IL-10. The effects of cell-surface components obtained by sonication of B. longum strains overall confirm the effects detected by stimulation of PBMCs with live cells, indicating that these components are important determinants of the immunomodulatory activity of B. longum. Genomic DNA of some strains stimulated the production of the Th1 and pro-inflammatory cytokines, interferon (IFN)-, and TNF-,, but not that of IL-10. None of the cell-free culture supernatants of the studied strains was able to induce TNF-, production, suggesting that the proinflammatory component of these strains is associated mainly with structural cell molecules. The results suggest that despite sharing certain features, some strains can perform a better functional role than others and their careful selection for therapeutic use is desirable. [source]