ovalbumin and Pneumococcal-Infections

Mycoplasma pneumoniae, an atypical human pathogen, has been associated with asthma initiation and exacerbation. Asthmatic patients have been reported to have higher carriage rates of M pneumoniae compared with nonasthmatic subjects and are at greater risk for invasive respiratory infections.. We sought to study whether prior allergen sensitization affects the host response to chronic bacterial infection.. BALB/cJ and IL-4 receptor α. Anti-M pneumoniae antibody responses were decreased in allergen-sensitized, M pneumoniae-infected animals compared with control animals, but OVA-specific IgG responses were unaffected. Similar decreases in anti-S pneumoniae antibody levels were found in OVA-sensitized animals. However, M pneumoniae, but not S pneumoniae, infection augmented anti-OVA IgE antibody responses. Loss of IL-4 receptor signaling partially restored anti-M pneumoniae antibody responses in IgG. An established type 2-biased host immune response impairs the host immune response to respiratory bacterial infection in a largely pathogen-independent manner. Some pathogens, such as M pneumoniae, can augment ongoing allergic responses and inhibit pulmonary type 2 cytokine responses and allergic airway hyperreactivity.

Topics: Allergens; Animals; Asthma; Cytokines; Immunoglobulin G; Lung; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; Pneumococcal Infections; Pneumonia, Mycoplasma; Receptors, Cell Surface; Respiratory Tract Infections

We previously demonstrated that intact, inactivated Streptococcus pneumoniae (unencapsulated strain R36A) inhibits IgG responses to a number of coimmunized soluble antigens (Ags). In this study, we investigated the mechanism of this inhibition and whether other extracellular bacteria exhibited similar effects. No inhibition was observed if R36A was given 24 h before or after immunization with soluble chicken ovalbumin (cOVA), indicating that R36A acts transiently during the initiation of the immune response. Using transgenic cOVA-specific CD4(+) T cells, we observed that R36A had no significant effect on T-cell activation (24 h) or generation of regulatory T cells (day 7) and only a modest effect on T-cell proliferation (48 to 96 h) in response to cOVA. However, R36A mediated a significant reduction in the formation of Ag-specific splenic germinal center T follicular helper (GC Tfh) and GC B cells and antibody-secreting cells in the spleen and bone marrow in response to cOVA or cOVA conjugated to 4-hydroxy-3-nitrophenylacetyl hapten (NP-cOVA). Of note, the inhibitory effect of intact R36A on the IgG anti-cOVA response could be reproduced using R36A-derived cell walls. In contrast to R36A, neither inactivated, unencapsulated, intact Neisseria meningitidis nor Streptococcus agalactiae inhibited the OVA-specific IgG response. These results suggest a novel immunosuppressive property within the cell wall of Streptococcus pneumoniae.

Topics: Animals; Antibodies, Bacterial; Antibody-Producing Cells; Bone Marrow; CD4-Positive T-Lymphocytes; Cell Proliferation; Cell Wall; Forkhead Transcription Factors; Germinal Center; Immunoglobulin G; Immunosuppressive Agents; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Ovalbumin; Plasma Cells; Pneumococcal Infections; Spleen; Streptococcus pneumoniae; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

In mice, allergic rhinitis augments the infectious and inflammatory response to Streptococcus pneumoniae-induced sinusitis.. To investigate the effects of cysteinyl leukotriene antagonism on the severity of bacterial infection.. We performed 3 parallel, placebo-controlled experiments. In the first, mice were ovalbumin sensitized and ovalbumin challenged to show the effects of montelukast on the allergic inflammation; in the second, we evaluated the effect of montelukast on S. pneumoniae infection; in the third, we used mice that were both allergic and infected. Montelukast was given starting 2 days after sensitization until the day before euthanasia. One day after drug treatment began, the mice were inoculated intranasally with S. pneumoniae in the infected groups. Nasal hypersensitivity was measured with histamine challenges before the first sensitization and on the day before euthanasia. On the fifth day after infection, mice were euthanized, nasal lavage was performed, bacteria were cultured, and inflammatory cells in the sinuses were quantified.. Mice that were infected only tended toward having increased bacterial counts from nasal lavage in the montelukast-treated group. The mice that were allergic and infected experienced significantly higher bacterial counts (P < .05). All 3 montelukast treatment groups had significantly decreased eosinophil counts as well as T-lymphocyte counts.. Montelukast reduces the manifestations of allergic rhinitis in mice. Surprisingly, montelukast led to an increase in bacterial growth in infected mice. This suggests an effect of the cysteinyl leukotrienes on the innate response to bacterial infection.

Topics: Acetates; Animals; Cyclopropanes; Female; Flow Cytometry; Hypersensitivity; Leukotriene Antagonists; Male; Mice; Mice, Inbred BALB C; Nasal Lavage Fluid; Ovalbumin; Pneumococcal Infections; Quinolines; Sinusitis; Streptococcus pneumoniae; Sulfides

To study the importance of ongoing allergen exposure and TH1/TH2 genetic background in augmented bacterial and inflammatory responses in allergic and infected mice.. BALB/c and C57BL/6 mice were made allergic to ovalbumin. After 1 day of intranasal allergen exposure, they were inoculated intranasally with Streptococcus pneumoniae. The numbers of bacteria and inflammatory cells in the sinuses were determined, and nasal responsiveness to histamine was assessed.. Infected BALB/c and C57BL/6 mice that received ongoing ovalbumin challenge following intraperitoneal sensitization showed significantly greater bacterial load and phagocyte level compared with the infected-only mice. Differences were diminished after the allergen challenge was stopped. Allergic and infected C57BL/6 mice showed fewer bacteria and phagocytes compared with the allergic and infected BALB/c mice. Surprisingly, in contrast to the nonallergenic C57BL/6 mice, the infected BALB/c mice showed a larger number of bacteria 28 days after infection.. Ongoing allergic reaction augments bacterial load in both BALB/c and C57BL/6 mice and induces nasal hyperreactivity to histamine. Allergic and infected C57BL/6 mice show less allergic inflammation and bacterial load compared with allergic and infected BALB/c mice. Stopping allergen exposure reduces the response. Infected BALB/c mice, which favor a TH2 response, were less able to clear infection than C57BL/6 mice, which favor a TH1 response. Inflammation and bacterial load are affected by genetic background of mice and ongoing allergen stimulation.

Topics: Allergens; Animals; Colony Count, Microbial; Hypersensitivity; Inflammation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nasal Cavity; Nasal Provocation Tests; Ovalbumin; Paranasal Sinuses; Pneumococcal Infections; Sinusitis; Streptococcus pneumoniae; Th1 Cells; Th2 Cells

Although it is not proven, one factor considered important in the development of sinusitis is allergic rhinitis.. The purpose of this study was to determine whether ongoing allergic rhinitis enhances the infection and inflammation associated with Streptococcus pneumoniae acute sinus infection.. BALB/c mice were sensitized to ovalbumin by intraperitoneal injection. After infection of the sinuses by S pneumoniae, either with or without concomitant administration of ovalbumin to induce allergic inflammation, mice were killed at various times and their heads were prepared for histologic evaluation of the sinuses.. Mice became allergic to ovalbumin and developed eosinophilia in the sinus and lung cavities in response to ovalbumin administration to each of the respective cavities. In comparison with controls, the mice with ongoing nasal allergic inflammation that were inoculated with S pneumoniae had significantly more bacteria recovered at sacrifice and had significantly more inflammation, as indicated by neutrophil, eosinophil, and mononuclear influx into the sinus mucosa. The percentage of the sinus area occupied by neutrophil clusters was also increased after infection in the allergic mice in comparison with the control mice.. Our data demonstrate that mice can be sensitized to ovalbumin and develop a localized allergic reaction in the skin, nose, or lung. An ongoing local allergic response augments bacterial infection in these animals. We also demonstrate that allergic sensitization alone, allergen exposure alone, or an allergic response at a distal site, the lung, does not augment the sinus infection.

Topics: Animals; Eosinophils; Female; Hypersensitivity; Male; Mice; Mice, Inbred BALB C; Mucous Membrane; Neutrophils; Ovalbumin; Pneumococcal Infections; Sinusitis

Humoral and cellular immune responses to several antigens were compared in control and hypercholesterolemic groups of monkeys. Chronic hypercholesterolemia, with concomitant hyperphospholipidemia and hypotriglyceridemia, was produced experimentally by feeding monkeys a high-fat, high-cholesterol diet. When studied prior to infection, hypercholesterolemic monkeys exhibited impaired development of precipitating antibodies against ovalbumin, enhanced sensitivity to tuberculin antigen (stimulated apparently by mycobacterial components in complete Freund adjuvant), and an increased rate of clearance of colloidal carbon from blood. During pneumococcal infection the ability of neutrophiles from hypercholesterolemic monkeys to reduce nitroblue tetrazolium dye showed an increase greater than that of control monkeys; both groups exhibited increased but comparable final clearance rates of colloidal carbon, although the increment of increase was smaller in hypercholesterolemic monkeys.

Topics: Animals; Antibody Formation; Disease Models, Animal; Haplorhini; Hypercholesterolemia; Macaca; Mononuclear Phagocyte System; Ovalbumin; Phospholipids; Pneumococcal Infections; Precipitin Tests; Triglycerides

Topics: Animals; Bacteria; Blood Proteins; Drug Resistance, Microbial; Escherichia coli; Hydrogen-Ion Concentration; Klebsiella; Klebsiella Infections; Mice; Microbial Sensitivity Tests; Ovalbumin; Pneumococcal Infections; Proline; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Tetracycline; Tetracyclines