muramidase and Salmonella-Infections--Animal

Environmental light cycles entrain circadian feeding behaviors in animals that produce rhythms in exposure to foodborne bacteria. Here, we show that the intestinal microbiota generates diurnal rhythms in innate immunity that synchronize with feeding rhythms to anticipate microbial exposure. Rhythmic expression of antimicrobial proteins was driven by daily rhythms in epithelial attachment by segmented filamentous bacteria (SFB), members of the mouse intestinal microbiota. Rhythmic SFB attachment was driven by the circadian clock through control of feeding rhythms. Mechanistically, rhythmic SFB attachment activated an immunological circuit involving group 3 innate lymphoid cells. This circuit triggered oscillations in epithelial STAT3 expression and activation that produced rhythmic antimicrobial protein expression and caused resistance to Salmonella Typhimurium infection to vary across the day-night cycle. Thus, host feeding rhythms synchronize with the microbiota to promote rhythms in intestinal innate immunity that anticipate exogenous microbial exposure.

Topics: Animals; Antimicrobial Cationic Peptides; Bacterial Adhesion; Cell Adhesion; Circadian Clocks; Circadian Rhythm; Epithelial Cells; Feeding Behavior; Gastrointestinal Microbiome; Immunity, Innate; Intestine, Small; Lymphocytes; Mice, Inbred C57BL; Muramidase; Pancreatitis-Associated Proteins; Salmonella Infections, Animal; Signal Transduction; STAT3 Transcription Factor

Recent studies link endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) to inflammatory bowel disease. Altered eIF2α phosphorylation (eIF2α-P), a regulatory hub of the UPR, was observed in mucosal tissue of patients with inflammatory bowel disease. In this study, we examined the mechanistic role of eIF2α-P in intestinal epithelial cell (IEC) function and intestinal homeostasis in mice.. We generated mice with villin-Cre-mediated conditional expression of nonphosphorylatable Ser51Ala mutant eIF2α in IECs (AA mice). We analyzed AA mice under normal conditions and on challenge with oral infection of Salmonella Typhimurium or dextran sulfate sodium-induced colitis.. Loss of eIF2α-P did not affect the normal proliferation or differentiation of IECs. However, AA mice expressed decreased secretory proteins including lysozyme, suggesting eIF2α-P is required for Paneth cell function. The ultrastructure of AA Paneth cells exhibited a reduced number of secretory granules, a fragmented ER, and distended mitochondria under normal conditions. UPR gene expression was defective in AA IECs. Translation of Paneth cell specific messenger RNAs encoding lysozyme and cryptidins was significantly defective leading to the observed granule-deficient phenotype, which was associated with reduced ribosomal recruitment of these messenger RNAs to the ER membrane. Consequently, AA mice were more susceptible to oral Salmonella infection and dextran sulfate sodium-induced colitis.. We conclude eIF2α phosphorylation is required for the normal function of intestinal Paneth cells and mucosal homeostasis by activating UPR signaling and promoting messenger RNA recruitment to the ER membrane for translation.

Topics: Animals; Apoptosis; Cell Differentiation; Cell Proliferation; Colitis; Dextran Sulfate; Disease Susceptibility; Endoplasmic Reticulum; Eukaryotic Initiation Factor-2; Homeostasis; Interferon-gamma; Mice; Mice, Inbred C3H; Mice, Transgenic; Molecular Chaperones; Muramidase; Paneth Cells; Phosphorylation; Protein Biosynthesis; Ribosomes; RNA, Messenger; Salmonella Infections, Animal; Secretory Vesicles; Signal Transduction; Stress, Physiological; Unfolded Protein Response

Antibiotics continue to be used as growth promoters in the poultry industry. Honeybee (Apis melifera) venom (HBV) possesses a number of beneficial biological activities, particularly for regulating the immune system. The aim of the present study was to evaluate the immunoprophylactic effects of HBV against Salmonella Gallinarum in broiler chicks as an initial step towards developing eco-friendly alternatives to reduce antibiotic use. HBV was administered using a spray technique. HBV improved body weight gain, particularly in the presence of infection. Moreover, HBV enhanced antibody production activity against formalin-killed S. Gallinarum. The CD4(+):CD8(+) T lymphocyte ratio, relative mRNA expression levels of interleukin-18 and interferon-γ, and serum lysozyme activity also increased following HBV administration before the infection period as well as during infection. HBV reinforced bacterial clearance and increased survivability against S. Gallinarum. Corresponding pathological analyses demonstrated that the HBV-sprayed group displayed mild and less severe abnormal changes compared with those in the control group. It was presumed that the prophylactic effects of HBV against S. Gallinarum were associated with its non-specific immune response stimulating activity. Thus, HBV may provide an alternative to reduce antibiotic use in the poultry industry.

Topics: Animals; Antibodies, Bacterial; Bee Venoms; Chickens; Colony Count, Microbial; Interferon-gamma; Interleukin-18; Lymphocyte Count; Muramidase; Poultry Diseases; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Salmonella enterica; Salmonella Infections, Animal

Paneth cells residing at the base of the small intestinal crypts contribute to the mucosal intestinal first line defense by secreting granules filled with antimicrobial polypeptides including lysozyme. These cells derive from the columnar intestinal stem cell located at position 0 and the transit amplifying cell located at position +4 in the crypts. We have previously shown that Salmonella enterica serovar Typhimurium (ST), a leading cause of gastrointestinal infections in humans, effects an overall reduction of lysozyme in the small intestine. To extend this work, we examined small-intestinal tissue sections at various time points after ST infection to quantify and localize expression of lysozyme and assess Paneth cell abundance, apoptosis, and the expression of Paneth cell differentiation markers. In response to infection with ST, the intestinal Paneth cell-specific lysozyme content, the number of lysozyme-positive Paneth cells, and the number of granules per Paneth cell decreased. However, this was accompanied by increases in the total number of Paneth cells and the frequency of mitotic events in crypts, by increased staining for the proliferation marker PCNA, primarily at the crypt side walls where the transit amplifying cell resides and not at the crypt base, and by apoptotic events in villi. Furthermore, we found a time-dependent upregulation of first β-catenin, followed by EphB3, and lastly Sox9 in response to ST, which was not observed after infection with a Salmonella pathogenicity island 1 mutant deficient in type III secretion. Our data strongly suggest that, in response to ST infection, a Paneth cell differentiation program is initiated that leads to an expansion of the Paneth cell population and that the transit amplifying cell is likely the main progenitor responder. Infection-induced expansion of the Paneth cell population may represent an acute intestinal inflammatory response similar to neutrophilia in systemic infection.

Topics: Animals; Cell Proliferation; Cytoplasm; Cytoplasmic Granules; Female; Intestinal Mucosa; Intestine, Small; Mice; Muramidase; Paneth Cells; Salmonella Infections, Animal; Salmonella typhimurium

Lysozymes are antimicrobial enzymes that perform a critical role in resisting infection in a wide-range of eukaryotes. However, using the nematode Caenorhabditis elegans as a model host we now demonstrate that deletion of the protist type lysozyme LYS-7 renders animals susceptible to killing by the fatal fungal human pathogen Cryptococcus neoformans, but, remarkably, enhances tolerance to the enteric bacteria Salmonella Typhimurium. This trade-off in immunological susceptibility in C. elegans is further mediated by the reciprocal activity of lys-7 and the tyrosine kinase abl-1. Together this implies a greater complexity in C. elegans innate immune function than previously thought.

Topics: Adaptation, Physiological; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cryptococcosis; Cryptococcus neoformans; Dosage Compensation, Genetic; Genes, Helminth; Humans; Muramidase; Mutation; Phenotype; Proto-Oncogene Proteins c-abl; Salmonella Infections, Animal; Salmonella typhimurium; Suppression, Genetic

Infection with Salmonella typhimurium can produce multiple organ dysfunctions. However, document concerning with gastric hemorrhagic ulcers occur in this infectious disease is lacking. The aim was to study modulation of gastric hemorrhagic ulcer by oxidative stress and mast cell histamine in S. typhimurium-infected rats. Additionally, the protective effects of drugs, such as ofloxacin, lysozyme chloride, ketotifen, ranitidine, and several antioxidants, including exogenous glutathione (GSH), allopurinol and dimethylsulfoxide (DMSO) were evaluated. Male Wistar rats were injected intrajejunally with a live culture of S. typhimurium (1 x 10(10) colony-forming units/rat) and followed by deprivation of food for 36 h. Age-matched control rats received sterilized vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or a simulated gastric juice containing 100 mM HCl, 17.4 mM pepsin and 54 mM NaCl. S. typhimurium caused aggravation of offensive factors, including enhancing gastric acid back-diffusion, mucosal lipid peroxide generation, histamine release, microvascular permeability and hemorrhagic ulcer, as well as an attenuation of defensive substances, such as mucosal GSH and mucus level. Intragastric irrigation of gastric juice caused further aggravation of these gastric biochemical parameters. This exacerbation of ulcerogenic factors was abolished by pretreatment of ofloxacin and lysozyme chloride. Antioxidants, such as reduced GSH, allopurinol and DMSO also produced significant (P < 0.05) amelioration of gastric damage in S. typhimurium infected rats. In conclusion, gastric oxidative stress and histamine play pivotal roles in the formation of hemorrhagic ulcers that were effectively ameliorated by ofloxacin, lysozyme chloride, ketotifen, ranitidine, diamine oxidase and various antioxidants in S. typhimurium-infected rats.

Topics: Allopurinol; Animals; Antioxidants; Dimethyl Sulfoxide; Disease Models, Animal; Gastric Juice; Gastric Mucosa; Gastrointestinal Hemorrhage; Glutathione; Histamine Release; Indomethacin; Lipid Peroxides; Male; Mast Cells; Muramidase; Ofloxacin; Oxidative Stress; Rats; Rats, Wistar; Salmonella Infections, Animal; Sodium Chloride; Stomach Ulcer; Therapeutic Irrigation

Infection of Salmonella typhimurium (Salmonella typhi) can lead to various organ diseases. This research first proposed that Salmonella typhi-infection could result in gastric oxidative stress and hemorrhagic ulcers that were ameliorated by ofloxacin, lysozyme chloride and several antioxidants, including exogenous glutathione (GSH), allopurinol and dimethylsulfoxide (DMSO). Male Wistar rats were given intrajejunally the live culture of Salmonella typhi [1 x 10(10) colony-forming unit (CFU)/rat] and followed by deprivation of food for 36 h. Age-matched control rats received vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or a simulated gastric juice containing 100 mM HCl, 17.4 mM pepsin and 54 mM NaCl. Infection of Salmonella typhi produced an aggravation of ulcerogenic factors, including enhancing gastric acid back-diffusion, mucosal lipid peroxide generation and hemorrhagic ulcer as well as an attenuation of mucosal GSH level. Intragastric irrigation of gastric juice caused further aggravation of these gastric biochemical parameters. This exacerbation of ulcerogenic factors was abolished by pretreatment of ofloxacin and lysozyme chloride. Antioxidants, such as reduced GSH, allopurinol and DMSO also produced significant (P<0.05) amelioration of gastric damage in Salmonella typhi-infected rats. In conclusion, infection of Salmonella typhi substantially caused gastric oxidative stress and disruption of gastric mucosal barriers, consequently resulted in gastric hemorrhagic ulcerations that were effectively ameliorated by ofloxacin, lysozyme chloride and various antioxidants.

Topics: Allopurinol; Animals; Anti-Infective Agents; Dimethyl Sulfoxide; Free Radical Scavengers; Gastric Juice; Gastric Mucosa; Gastrointestinal Hemorrhage; Glutathione; Lipid Peroxides; Male; Muramidase; Ofloxacin; Oxidative Stress; Rats; Rats, Wistar; Salmonella Infections, Animal; Salmonella typhimurium; Sodium Chloride; Stomach Ulcer; Therapeutic Irrigation

Paneth cells, highly secretory epithelial cells found at the bases of small intestinal crypts, release a variety of microbicidal molecules, including alpha-defensins and lysozyme. The secretion of antimicrobials by Paneth cells is thought to be important in mucosal host defense against invasion by enteric pathogens. We explored whether enteric pathogens can interfere with this arm of defense. We found that oral inoculation of mice with wild-type Salmonella enterica serovar Typhimurium decreases the expression of alpha-defensins (called cryptdins in mice) and lysozyme. Oral inoculation with Salmonella serovar Typhimurium strains that are heat killed, lack the PhoP regulon, and lack the SPI1 type III secretion system or with Listeria monocytogenes does not have this effect. Salmonella may gain a specific survival advantage in the intestinal lumen by decreasing the expression of microbicidal peptides in Paneth cells through direct interactions between Salmonella and the small intestinal epithelium.

Topics: Animals; Anti-Bacterial Agents; Female; Intestinal Diseases; Intestine, Small; Mice; Mitogen-Activated Protein Kinases; Muramidase; p38 Mitogen-Activated Protein Kinases; Paneth Cells; Protein Precursors; RNA, Messenger; Salmonella Infections, Animal; Salmonella typhimurium

Efficacy of the combined therapy of experimental salmonellosis was studied on albino rats with using ampicillin, gentamicin, tetracycline and immunomodulators such as levamisole and quadevite. The influence of the combined chemoimmunotherapy on the indices of the nonspecific resistance of the animals i.e. the titers of lysozyme and beta-lysines, the complement activity and the blood serum bactericidal index was investigated. An increase in the survival of the animals exposed to the combinations of tetracycline with levamisole and quadevite by comparison with the animal survival after the monotherapy was revealed. The combinations of gentamicin with quadevite and tetracycline with the immunomodulators significantly increased the blood serum bactericidal index.

Topics: Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Blood Bactericidal Activity; Drug Therapy, Combination; Lysine; Muramidase; Rats; Salmonella Infections, Animal; Salmonella typhimurium

Experiments on noninbred white mice have revealed that in the animals infected with S. moscow secondary immunodeficiency develops, which is manifested by a significant decrease in the activity of the bactericidal system of peripheral blood granular leukocytes. Simultaneously, the content of myeloperoxidase in the blood neutrophils of infected mice decreases 1.4 times and the content of lysozyme in these neutrophils decreases 2 times. Such changes are the consequence of an increase in the secretory activity of cells, occurring in the process of the development of Salmonella infection.

Topics: Animals; Blood Bactericidal Activity; Immunologic Deficiency Syndromes; Mice; Muramidase; Neutrophils; Peroxidase; Salmonella Infections, Animal; Time Factors

Investigations were carried out on the protective action of therapeutic doses of levamisole (Pharmachim) on mice with a LD100 Salmonella gallinarum infection. Studied was also the effect of levamisole on the immunologic response of guinea pigs infected with Salmonella cholerae suis. It was found that therapeutic amounts of 3 mg/kg levamisole applied to mice following respective patterns protected them against a lethal dose of S. gallinarum. The animals showed enhanced resistance to the infection--20 to 50 per cent of them survived as against 100 per cent mortality with the controls. The guinea pigs showed upon treatment with levamisole certain changes with some of the factors of unspecific response--enhanced phagocytic and lysozyme activity as judged by the development of infection with a S. cholerae suis culture. At the same time the agglutinin titer that substantiated the immunologic response was negligibly changed as compared to the controls. On the base of the results obtained an attempt was made to elucidate the mechanism of the protective action of levamisole.

Topics: Agglutinins; Animals; Antigen-Antibody Reactions; Drug Evaluation, Preclinical; Guinea Pigs; Levamisole; Mice; Muramidase; Phagocytosis; Salmonella Infections, Animal

Topics: Animals; Antibodies; Antibody Formation; Blood Bactericidal Activity; Cell Count; Chick Embryo; Dose-Response Relationship, Drug; Fibroblasts; Immunity; In Vitro Techniques; Interferon Inducers; Interferons; Mice; Muramidase; Phagocytes; Phagocytosis; Properdin; Protein Biosynthesis; RNA; Salmonella Infections, Animal; Staphylococcal Infections; Staphylococcus; Time Factors; Toxins, Biological; Yeasts

Topics: Animals; Disease Models, Animal; Drug Synergism; Encephalomyocarditis virus; Female; Injections, Intraperitoneal; Injections, Intravenous; Leukocyte Count; Male; Mice; Muramidase; Orthomyxoviridae; Orthomyxoviridae Infections; Phagocytosis; Phenanthrenes; Poliomyelitis; Salmonella Infections, Animal; Salmonella typhimurium; Staphylococcal Infections; Staphylococcus

Topics: Agglutination Tests; Animals; Muramidase; Peptide Hydrolases; Poultry Diseases; Ribonucleases; Salmonella Infections, Animal; Tissue Extracts

Topics: Animals; Calcium Chloride; Immunity; Mice; Muramidase; Peptides; Pharmacology; Proteus Infections; Research; Salmonella Infections; Salmonella Infections, Animal; Staphylococcal Infections; Thymus Gland; Trypsin; Virulence