ovalbumin and Bacterial-Infections

Topics: Animals; Animals, Newborn; Bacterial Infections; Blood Bactericidal Activity; Body Temperature; Chick Embryo; Chickens; Egg Proteins; Egg Shell; Female; Infections; Intestines; Muramidase; Mycoses; Ovalbumin; Phagocytosis; Skin; Transferrin; Virus Diseases; Vitelline Membrane

Acute exacerbations of asthma represent a major burden of disease and are often caused by respiratory infections. Viral infections are recognized as significant triggers of exacerbations; however, less is understood about the how microbial bioproducts such as the endotoxin (lipopolysaccharide (LPS)) trigger episodes. Indeed, increased levels of LPS have been linked to asthma onset, severity and steroid resistance.. The goal of this study was to identify mechanisms underlying bacterial-induced exacerbations by employing LPS as a surrogate for infection.. We developed a mouse model of LPS-induced exacerbation on the background of pre-existing type-2 allergic airway disease (AAD).. LPS-induced exacerbation was characterized by steroid-resistant airway hyperresponsiveness (AHR) and an exaggerated inflammatory response distinguished by increased numbers of infiltrating neutrophils/macrophages and elevated production of lung inflammatory cytokines, including TNFα, IFNγ, IL-27 and MCP-1. Expression of the type-2 associated inflammatory factors such as IL-5 and IL-13 were elevated in AAD but not altered by LPS exposure. Furthermore, AHR and airway inflammation were no longer suppressed by corticosteroid (dexamethasone) treatment after LPS exposure. Depletion of pulmonary macrophages by administration of 2-chloroadenosine into the lungs suppressed AHR and reduced IL-13, TNFα and IFNγ expression. Blocking IL-13 function, through either IL-13-deficiency or administration of specific blocking antibodies, also suppressed AHR and airway inflammation.. We present evidence that IL-13 and innate immune pathways (in particular pulmonary macrophages) contribute to LPS-induced exacerbation of pre-existing AAD and provide insight into the complex molecular processes potentially underlying microbial-induced exacerbations.

Topics: Airway Resistance; Animals; Asthma; Bacterial Infections; Bronchoalveolar Lavage Fluid; Chemokine CCL2; Cytokines; Dexamethasone; Disease Models, Animal; Disease Progression; Drug Resistance; Glucocorticoids; Interferon-gamma; Interleukin-13; Interleukins; Lipopolysaccharides; Macrophage Activation; Macrophages, Alveolar; Mice; Mucin 5AC; Ovalbumin; Respiratory Hypersensitivity; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha

Dextran was used to explore a novel method of enhancing an immune response against T-cell independent type 2 (TI-2) polysaccharide antigens, because of its suitability as a model for the immunogenecity of many TI-2 polysaccharide antigens and its high affinity to SIGN-R1. Here we showed that the primary immune response of IgM, IgG3, and IgG2b was enhanced by dextran in SIGN-R1 knock-out (KO) mice, further evoking the induction of a secondary immune response to IgG2b in parallel. On the other hand, an immune response of IgG1 and IgG2b against T-cell dependent (TD) antigen was strongly enhanced by the administration of ovalbumin (OVA) in SIGN-R1 KO mice. These results indicate that SIGN-R1 is critical in the regulation of immune responses. Therefore, our study suggests that inhibition of TI-2 polysaccharide antigen uptake in SIGN-R1(+) macrophages contributes to the development of novel vaccination strategies against TI-2 polysaccharide antigens.

Topics: Animals; Antigens, T-Independent; Bacterial Infections; Cell Adhesion Molecules; Dextrans; Female; Fluorescein-5-isothiocyanate; Immunity, Humoral; Immunoglobulin G; Immunoglobulin M; Lectins, C-Type; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Receptors, Cell Surface; Receptors, Immunologic; Spleen; T-Lymphocytes; Vaccination

The notion that the mucosal immune system maintains a tolerogenic response to harmless Ags while continually being challenged with microbial products seems an enigma. The aim of this study was to unravel mechanisms that are involved in regulating the development of tolerance under constant microbial pressure. The tolerogenic response to Ags administered via the nasal mucosa is dependent on the organized lymphoid tissue of the cervical lymph nodes (LN). We show that cervical LN differentially express secretory leukoprotease inhibitor (SLPI) compared with peripheral LN. SLPI was expressed by dendritic cells (DCs) and because SLPI is known to suppress LPS responsiveness, it was hypothesized that its expression in mucosal DCs may be required to regulate cellular activation to microbial products. Indeed, compared with wild-type controls, bone marrow-derived DCs from SLPI(-/-) mice released more inflammatory cytokines and enhanced T cell proliferation after stimulation with low dose LPS. This increased sensitivity to LPS was accompanied by increased NF-kappaB p65 activation in SLPI(-/-) DCs. In vivo, nasal application of OVA with LPS to SLPI(-/-) mice resulted in enhanced DC activation in the cervical LN reflected by increased costimulatory molecule expression and release of inflammatory cytokines. This led to failure to maintain tolerance to nasal OVA application in the presence of low doses of LPS. We propose that expression of SLPI functions as a rheostat by controlling the level of bacterial stimuli that induce mucosal DC activation. As such, it regulates the quality of the ensuing Ag-specific immune response in the mucosa draining LN.

Topics: Animals; Antigens; Bacterial Infections; Cell Proliferation; Cytokines; Dendritic Cells; Gene Expression Regulation; Immune Tolerance; Immunity, Mucosal; Inflammation; Lipopolysaccharides; Lymph Nodes; Mice; Mice, Inbred BALB C; Nasal Mucosa; Organ Specificity; Ovalbumin; Secretory Leukocyte Peptidase Inhibitor; T-Lymphocytes; Transcription Factor RelA

Previously, we showed that an ongoing nasal allergic response augmented bacterial sinusitis in mice. In those experiments mice were sensitized to ovalbumin (OVA) by means of intraperitoneal injections of OVA-alum and then exposed to OVA intranasally before being infected with Streptococcus pneumoniae.. We sought to study the importance of TH2 cells and to eliminate potential alum effects.. In this study we sensitized mice by adoptively transferring OVA-specific TH2- or TH1-skewed cells.. TH2 passive sensitization followed by intranasal OVA showed a robust local eosinophilic response (5-fold increase) compared with that seen in mice with only TH2 passive sensitization alone (P <.001). Mice with TH2 passive sensitization and intranasal OVA exposure followed by infection showed an increase in the number of recovered S pneumoniae (P <.05) and an increase in sinus inflammation compared with that seen in those with infection alone (P <.01). In contrast, mice passively sensitized with TH1 followed by intranasal OVA exposure and infection showed no significant increase in the recovery of S pneumoniae and sinus inflammation compared with those with infection alone.. These data support the importance of antigen-stimulated TH2 cells in the augmented response to infection in allergic mice. Whether the increased infection is related to the direct effect of TH2 cells and their cytokines or subsequent recruitment of other cells, such as eosinophils, will be determined in further studies.

Topics: Acute Disease; Adoptive Transfer; Animals; Bacterial Infections; Mice; Mice, Inbred BALB C; Ovalbumin; Sinusitis; Th1 Cells; Th2 Cells

Infant rats primed during the first week of life with soluble antigen displayed adult-equivalent levels of T-helper 2 (Th2)-dependent immunological memory development as revealed by production of secondary immunoglobulin G1 (IgG1) antibody responses to subsequent challenge, but in contrast to adults failed to prime for Th1-dependent IgG2b responses. We demonstrate that this Th2 bias in immune function can be redressed by oral administration to neonates of a bacterial extract (Broncho-Vaxom OM-85) comprising lyophilized fractions of several common respiratory tract bacterial pathogens. Animals given OM-85 displayed a selective upregulation in primary and secondary IgG2b responses, accompanied by increased gamma interferon and decreased interleukin-4 production (both antigen specific and polyclonal), and increased capacity for development of Th1-dependent delayed hypersensitivity to the challenge antigen. We hypothesize that the bacterial extract functions via enhancement of the process of postnatal maturation of Th1 function, which is normally driven by stimuli from the gastrointestinal commensal microflora.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacteria; Bacterial Infections; Cell Extracts; Disease Models, Animal; Hypersensitivity, Delayed; Immunization; Immunocompromised Host; Immunoglobulin G; Ovalbumin; Rats; Respiratory Tract Infections; T-Lymphocytes; Th1 Cells

Topics: Analysis of Variance; Animal Nutritional Physiological Phenomena; Animals; Bacterial Infections; Birth Weight; Colostrum; Female; Immunity, Maternally-Acquired; Immunoglobulins; Intestinal Absorption; Male; Nutrition Disorders; Orchiectomy; Ovalbumin; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Sheep; Stress, Physiological

An intestinal immunisation procedure involving systemic priming and oral boosting was investigated in lambs with a view to providing vaccination control of enteritis in young animals. The procedure stimulated the appearance of antibody-containing cells of IgA specificity in the intestine and lambs immunised in this way with a bacterial vaccine were protected against subsequent challenge with live enteropathogenic bacteria. This immunisation regime therefore provides a useful method for the stimulation of IgA immunity in the intestine of ruminants and it is anticipated that it will have general application to a variety of enteric diseases.

Topics: Animals; Antibodies, Bacterial; Bacterial Infections; Enteritis; Female; Immunization; Immunization Schedule; Models, Biological; Ovalbumin; Salmonella Infections, Animal; Salmonella typhimurium; Sheep; Sheep Diseases