ROLE OF IL-6 IN THE PATHOGENESIS OF YERSINIA ENTEROCOLITICA INFECTION
Peter H Dube
University Of Texas Hlth Sci Ctr San Ant, San Antonio, Tx 78229
Grant 5R01AI067716-03 from National Institute Of Allergy And Infectious Diseases
Abstract: Food and water borne infectious diseases are a significant source of morbidity and mortality world-wide. Children are especially at risk from these infections. Although often assumed to be only a problem in developing areas of the world, bacterial infections of the gastro-intestinal tract remain a serious source of disease in the US. Our long-term goal is to understand both host-response and host pathogen interactions in the gut to Yersinia enterocolitica that lead to resolution of infection or to pathology. Y. enterocolitica is an excellent pathogen to use in our studies as it has served as one of the paradigms of bacterial infectious diseases. In this proposal we expand our studies to look at the role of IL-6 in the modulation of the host response during Y. enterocolitica infection. We hypothesize that IL-6 may be a crucial regulator of inflammatory responses to infection by influencing the cytokine response of host cells involved in response to Y. enterocolitica infection. We also hypothesize that the IL-6 mediated tempering of inflammatory responses may be triggered by Y. enterocolitica encoded molecules. To test these hypotheses we propose the following specific aims 1) Identify the cells producing IL-6 in response to Y. enterocolitica infection and 2) the cells responding to IL-6 during infection in the Peyer´s patch, mesenteric lymph node, and spleen. These data will give us insight into which host cells are modulating the host response to infection. 3) Test the contribution of the IL-6 modulated cytokines to the immunopathogenesis of intestinal yersiniosis. Mice deficient in IL-6 have distinct cytokine expression profiles and many of these cytokines are critical to the resolution of disease but it is unknown how mis-regulation of these cytokines contributes to pathology. These data will explore the connection between IL-6 mediated modulation of the immune response and Yersinia virulence. Altogether, these data will give us insight into how IL-6 contributes to the pathogenesis of Yersinia infection and how immune pathologies are prevented during self limiting infections. These data may provide insight into the etiology of chronic intestinal inflammation
Keywords: 0-11 years old; Acute; Anti-Inflammatories; Anti-Inflammatory Agents; Anti-inflammatory; Antiinflammatories; Antiinflammatory Agents; Area; B cell differentiation factor; B cell stimulating factor 2; B-Cell Differentiation Factor-2; B-Cell Stimulatory Factor-2; BCDF; BSF-2; BSF2; BSF2 (B cell stimulating factor 2); Back; Bacteria; Bacterial Infections; Causality; Cells; Child; Child Youth; Children (0-21); Chronic; Clinical; Communicable Diseases; Complex; Data; Differentiation Factor, B-Cell; Disease; Disorder; Dorsum; Etiology; Expression Profiling; Expression Signature; Food; Gastrointestinal Diseases; Gastrointestinal Diseases and Manifestations; Goals; Gut Inflammation; HPGF; Hepatocyte-Stimulating Factor; Human, Child; Hybridoma Growth Factor; Hydrogen Oxide; IFN-beta 2; IFNB2; IL-1; IL-1 inhibitor, urine; IL-1ra; IL-6; IL1; IL1 febrile inhibitor; IL1RN; IL6 Protein; INFLM; Immune; Immune response; Immune system; In Vitro; Infection; Infectious Disease Pathway; Infectious Diseases; Infectious Diseases and Manifestations; Infectious Disorder; Inflammation; Inflammatory; Inflammatory Diseases of the Intestinal Tract; Inflammatory Response; Inflammatory disease of the intestine; Inflammatory disorder of the intestine; Interleukin 6 (Interferon, Beta 2); Interleukin I; Interleukin-1; Interleukin-1 Receptor Antagonist; Interleukin-6; Intestinal; Intestinal Inflammation; Intestines; Investigators; Knowledge; Lead; Learning; Lymph node proper; Lymphocyte-Stimulating Hormone; MGI-2; Macrophage Cell Factor; Mammals, Mice; Mediating; Mesenteric; Mesentery; Mice; Modeling; Molecular; Molecular Fingerprinting; Molecular Profiling; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Murine; Mus; Myeloid Differentiation-Inducing Protein; P. pseudotuberculosis; Pasteurella pseudotuberculosis; Pathogenesis; Pathogenicity Factors; Pathology; Pb element; Peyer`s Patches; Plague; Plasmacytoma Growth Factor; Plasmids; Play; Programs (PT); Programs [Publication Type]; Regulation; Research Personnel; Researchers; Resolution; Reticuloendothelial System, Lymph Node; Reticuloendothelial System, Spleen; Risk; Role; Source; Spleen; Staging; Structure of aggregated lymphoid follicle of small intestine; Syndrome; T Helper Factor; T-Cells; T-Lymphocyte; Testing; Thymus-Dependent Lymphocytes; Type III Secretion System; Type III Secretion System Pathway; Virulence; Virulence Factors; Water; Y. enterocolitica; Y. pseudotuberculosis; Y.enterocolitica; Yersinia; Yersinia enterocolitica; Yersinia infections; Yersinia pestis disease; Yersinia pseudotuberculosis; anakinra; bacterial disease; body system, allergic/immunologic; bowel; children; cytokine; disease causation; disease etiology; disease/disorder; disease/disorder etiology; disorder etiology; enteric pathogen; feeding; gastrointestinal disorder; heavy metal Pb; heavy metal lead; host response; immunoresponse; in vivo; infection mouth; inhibitor; inhibitor/antagonist; insight; interferon beta 2; interleukin 1 inhibitor, urine; interleukin 1 receptor antagonist protein; lymph gland; lymph nodes; lymphocyte activating factor; molecuar profile; molecular signature; oral infection; oral infectious; organ system, allergic/immunologic; pathogen; prevent; preventing; programs; response; social role; thymus derived lymphocyte; urine-derived IL1 inhibitor; youngster
Project start date: 2007-06-01
Project end date: 2012-05-31
Budget start date: 1-JUN-2009
Budget end date: 31-MAY-2010
PFA/PA: PA-04-119
5R01AI067716-03 (2009): $358065
Sponsored Links Excellgen http://Excellgen.com
ROLE OF IL-6 IN THE PATHOGENESIS OF YERSINIA ENTEROCOLITICA INFECTION
Peter H Dube
University Of Texas Hlth Sci Ctr San Ant, San Antonio, Tx 78229
Grant 5R01AI067716-04 from National Institute Of Allergy And Infectious Diseases
Abstract: Food and water borne infectious diseases are a significant source of morbidity and mortality world-wide. Children are especially at risk from these infections. Although often assumed to be only a problem in developing areas of the world, bacterial infections of the gastro-intestinal tract remain a serious source of disease in the US. Our long-term goal is to understand both host-response and host pathogen interactions in the gut to Yersinia enterocolitica that lead to resolution of infection or to pathology. Y. enterocolitica is an excellent pathogen to use in our studies as it has served as one of the paradigms of bacterial infectious diseases. In this proposal we expand our studies to look at the role of IL-6 in the modulation of the host response during Y. enterocolitica infection. We hypothesize that IL-6 may be a crucial regulator of inflammatory responses to infection by influencing the cytokine response of host cells involved in response to Y. enterocolitica infection. We also hypothesize that the IL-6 mediated tempering of inflammatory responses may be triggered by Y. enterocolitica encoded molecules. To test these hypotheses we propose the following specific aims 1) Identify the cells producing IL-6 in response to Y. enterocolitica infection and 2) the cells responding to IL-6 during infection in the Peyer´s patch, mesenteric lymph node, and spleen. These data will give us insight into which host cells are modulating the host response to infection. 3) Test the contribution of the IL-6 modulated cytokines to the immunopathogenesis of intestinal yersiniosis. Mice deficient in IL-6 have distinct cytokine expression profiles and many of these cytokines are critical to the resolution of disease but it is unknown how mis-regulation of these cytokines contributes to pathology. These data will explore the connection between IL-6 mediated modulation of the immune response and Yersinia virulence. Altogether, these data will give us insight into how IL-6 contributes to the pathogenesis of Yersinia infection and how immune pathologies are prevented during self limiting infections. These data may provide insight into the etiology of chronic intestinal inflammation
Keywords: 0-11 years old; Acute; Anti-Inflammatories; Anti-Inflammatory Agents; Anti-inflammatory; Antiinflammatories; Antiinflammatory Agents; Area; B cell differentiation factor; B cell stimulating factor 2; B-Cell Differentiation Factor-2; B-Cell Stimulatory Factor-2; BCDF; BSF-2; BSF2; BSF2 (B cell stimulating factor 2); Back; Bacteria; Bacterial Infections; Causality; Cells; Child; Child Youth; Children (0-21); Chronic; Clinical; Communicable Diseases; Complex; Data; Differentiation Factor, B-Cell; Disease; Disorder; Dorsum; Etiology; Expression Profiling; Expression Signature; Food; Gastrointestinal Diseases; Gastrointestinal Diseases and Manifestations; Goals; Gut Inflammation; HPGF; Hepatocyte-Stimulating Factor; Human, Child; Hybridoma Growth Factor; Hydrogen Oxide; IFN-beta 2; IFNB2; IL-1; IL-1 inhibitor, urine; IL-1ra; IL-6; IL1; IL1 febrile inhibitor; IL1RN; IL6 Protein; INFLM; Immune; Immune response; Immune system; In Vitro; Infection; Infectious Disease Pathway; Infectious Diseases; Infectious Diseases and Manifestations; Infectious Disorder; Inflammation; Inflammatory; Inflammatory Diseases of the Intestinal Tract; Inflammatory Response; Inflammatory disease of the intestine; Inflammatory disorder of the intestine; Interleukin 6 (Interferon, Beta 2); Interleukin I; Interleukin-1; Interleukin-1 Receptor Antagonist; Interleukin-6; Intestinal; Intestinal Inflammation; Intestines; Investigators; Knowledge; Lead; Learning; Lymph node proper; Lymphocyte-Stimulating Hormone; MGI-2; Macrophage Cell Factor; Mammals, Mice; Mediating; Mesenteric; Mesentery; Mice; Modeling; Molecular; Molecular Fingerprinting; Molecular Profiling; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Murine; Mus; Myeloid Differentiation-Inducing Protein; P. pseudotuberculosis; Pasteurella pseudotuberculosis; Pathogenesis; Pathogenicity Factors; Pathology; Pb element; Peyer`s Patches; Plague; Plasmacytoma Growth Factor; Plasmids; Play; Programs (PT); Programs [Publication Type]; Regulation; Research Personnel; Researchers; Resolution; Reticuloendothelial System, Lymph Node; Reticuloendothelial System, Spleen; Risk; Role; Source; Spleen; Staging; Structure of aggregated lymphoid follicle of small intestine; Syndrome; T Helper Factor; T cell response; Testing; Type III Secretion System; Type III Secretion System Pathway; Virulence; Virulence Factors; Water; Y. enterocolitica; Y. pseudotuberculosis; Y.enterocolitica; Yersinia; Yersinia enterocolitica; Yersinia infections; Yersinia pestis disease; Yersinia pseudotuberculosis; anakinra; bacterial disease; body system, allergic/immunologic; bowel; children; cytokine; disease causation; disease etiology; disease/disorder; disease/disorder etiology; disorder etiology; enteric pathogen; feeding; gastrointestinal disorder; heavy metal Pb; heavy metal lead; host response; immunoresponse; in vivo; infection mouth; inhibitor; inhibitor/antagonist; insight; interferon beta 2; interleukin 1 inhibitor, urine; interleukin 1 receptor antagonist protein; lymph gland; lymph nodes; lymphocyte activating factor; molecuar profile; molecular signature; oral infection; oral infectious; organ system, allergic/immunologic; pathogen; prevent; preventing; programs; response; social role; urine-derived IL1 inhibitor; youngster
Project start date: 2007-06-01
Project end date: 2012-05-31
Budget start date: 1-JUN-2010
Budget end date: 31-MAY-2011
PFA/PA: PA-04-119
5R01AI067716-04 (2010): $354485
Grants awarded to Peter H Dube
HOST RESPONSE TO YERSINIA PESTIS INFECTION
Peter H Dube
University Of Texas Hlth Sci Ctr San Ant, San Antonio, Tx 78229
Grant 5R21AI060789-02 from National Institute Of Allergy And Infectious Diseases
Abstract: Yersinia pestis is an incidental human pathogen that is the causative agent of plague. Historically plague has been a significant source of human morbidity and mortality. In areas where plague is endemic in rodent populations humans are still at significant risk. Plague may re-emerge as a significant danger to human health due to the recent identification of multi-drug resistant strains of Y. pestis and the possibility that Y. pestis may be used as an agent of biological terrorism. Although plague has been a major health problem for more than 1500 years, relatively nothing is known about the pathogenesis of Y. pestis infection. In particular, detailed molecular data on the host response to Y. pestis infection is lacking. This data is crucial for the development of new treatments and may significantly improve vaccine strategies. Using the mouse model of Y. enterocolitica infection combined with microarray analysis of infected tissues we have gained significant insight into the host response to the enteropathogenic Yersiniae. These studies have improved our understanding of the molecular basis of the host response to Y. enterocolitica and should serve as a template for an analysis of the host response to Y. pestis. Based on our previous investigations we hypothesize that Y. pestis infection induces the expression of genes encoding immunomodulatory proteins (cytokines, chemokines, proteases, and immune effectors) and the expression of these proteins dictates the outcome of the infection. To test these hypotheses we propose 1) A comprehensive analysis of host gene expression to Y. pestis infection 2) Analysis of the effect of defined host deficiencies on the immune response to Y. pestis infection in vivo. We will utilize microarray analysis of tissues from Y. pestis infected mice including defined (cytokines) host mutants to study the host response to plague. Additionally the roles of cytokines (TARC, TGF-beta, TNF-alpha, IL-13, IL-6, IL-10) will be examined using the mouse model of infection. These studies will improve our understanding of the host immune response to Y. pestis infection
Keywords: A-152E5.3; ABCD-2; Animals; Anti-Inflammatories; Anti-Inflammatory Agents; Anti-inflammatory; Antiinflammatories; Antiinflammatory Agents; Area; B cell differentiation factor; B cell stimulating factor 2; B-Cell Differentiation Factor-2; B-Cell Stimulatory Factor-2; BCDF; BSF-2; BSF2; BSF2 (B cell stimulating factor 2); Biological Terrorism; Bioterrorism; Body Tissues; Bone-Derived Transforming Growth Factor; CCL17; CCL17 gene; CSIF; CSIF-10; Cachectin; Cachectin-Tumor Necrosis Factor; Cell/Tissue, Immunohistochemistry; Cells; Characteristics; Cytokine Synthesis Inhibitory Factor; Cytokine formation-inhibiting factor (mouse clone F115 protein moiety reduced); Cytokines, Chemotactic; Data; Development; Differentiation Factor, B-Cell; Disease; Disorder; Drug Resistance, Multiple; Drug Resistant, Multiple; ELISA; Endopeptidases; Enzyme-Linked Immunosorbent Assay; Esteroproteases; Expression Profiling; Expression Signature; Gene Expression; HPGF; Health; Hepatocyte-Stimulating Factor; Homologous Chemotactic Cytokines; Hour; Human; Human, General; Hybridoma Growth Factor; IFN-beta 2; IFNB2; IHC; IL-10; IL-13; IL-6; IL10; IL10A; IL13; IL6 Protein; Immune; Immune response; Immunohistochemistry; Immunohistochemistry Staining Method; Incidence; Infection; Infiltration; Inflammatory; Inflammatory Response; Intercrines; Interleukin 10 Precursor; Interleukin 6 (Interferon, Beta 2); Interleukin-10; Interleukin-13; Interleukin-6; Investigation; Investigators; Lung; MGI-2; Madagascar; Malagasy Republic; Mammals, Mice; Mammals, Rodents; Man (Taxonomy); Man, Modern; Measures; Mice; Microarray Analysis; Microarray-Based Analysis; Milk Growth Factor; Modeling; Molecular; Molecular Fingerprinting; Molecular Profiling; Mortality; Mortality Vital Statistics; Multi-Drug Resistance; Multidrug Resistance; Murine; Mus; Myeloid Differentiation-Inducing Protein; Numbers; Outcome; P. pseudotuberculosis; PCR; Pasteurella pestis; Pasteurella pseudotuberculosis; Pathogenesis; Pathogenicity Factors; Peptidases; Peptide Hydrolases; Peptide Peptidohydrolases; Plague; Plasmacytoma Growth Factor; Platelet Transforming Growth Factor; Pneumonia; Pneumonic Plague; Pneumonitis; Polymerase Chain Reaction; Population; Proteases; Proteinases; Proteins; Proteolytic Enzyme; Proteolytic Enzymes; Public Health; Pulmonary Inflammation; Relative; Relative (related person); Research Personnel; Researchers; Resistance to Multi-drug; Resistance to Multidrug; Resistance to Multiple Drug; Resistant to Multiple Drug; Resistant to multi-drug; Resistant to multidrug; Respiratory Infections; Respiratory System, Lung; Respiratory Tract Infections; Risk; Rodent; Rodentia; Rodentias; Role; SCYA17; SIS cytokines; Source; TARC; TGF B; TGF-beta; TGFbeta; TNF; TNF Alpha; TNF protein, human; TNF superfamily, member 2 protein, human; TNF-2 protein, human; TNF-alpha; TNFA; TNFSF2 protein, human; Testing; Time; Tissues; Transforming Growth Factor beta; Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha (macrophage-derived); Vaccines; Virulence Factors; Y. enterocolitica; Y. pestis; Y. pseudotuberculosis; Y.enterocolitica; Y.pestis; Yersinia; Yersinia enterocolitica; Yersinia pestis; Yersinia pestis disease; Yersinia pseudotuberculosis; base; chemoattractant cytokine; chemokine; cytokine; disease/disorder; enteric pathogen; gene product; host response; human TNF protein; human morbidity; immunoresponse; improved; in vivo; insight; interferon beta 2; microarray technology; molecuar profile; molecular signature; mouse model; multi-drug resistant; multidrug resistant; mutant; pandemic; pandemic disease; pathogen; protease; protein expression; proteinase; public health medicine (field); pulmonary; response; social role; tool; tumor necrosis factor, human; tumor necrosis factor-2 protein, human; tumor necrosis factor-alpha promoter allele-2 protein, human
Project start date: 2007-09-20
Project end date: 2010-08-31
Budget start date: 1-SEP-2008
Budget end date: 31-AUG-2010
PFA/PA: PA-04-119
5R21AI060789-02 (2008): $0
1R21AI060789-01A2 (2007): $292000
Role Of IL-6 In The Pathogenesis Of Y.enterocolitica Infection
Peter H Dube, Assistant Professor
University Of Texas Hlth Sci Ctr San Ant San Antonio, Tx 78229
Grant 1R01AI067716-01A2 from National Institute Of Allergy And Infectious Diseases IRG: HIBP
Abstract: Food and water borne infectious diseases are a significant source of morbidity and mortality world-wide. Children are especially at risk from these infections. Although often assumed to be only a problem in developing areas of the world, bacterial infections of the gastro-intestinal tract remain a serious source of disease in the US. Our long-term goal is to understand both host-response and host pathogen interactions in the gut to Yersinia enterocolitica that lead to resolution of infection or to pathology. Y. enterocolitica is an excellent pathogen to use in our studies as it has served as one of the paradigms of bacterial infectious diseases. In this proposal we expand our studies to look at the role of IL-6 in the modulation of the host response during Y. enterocolitica infection. We hypothesize that IL-6 may be a crucial regulator of inflammatory responses to infection by influencing the cytokine response of host cells involved in response to Y. enterocolitica infection. We also hypothesize that the IL-6 mediated tempering of inflammatory responses may be triggered by Y. enterocolitica encoded molecules. To test these hypotheses we propose the following specific aims 1) Identify the cells producing IL-6 in response to Y. enterocolitica infection and 2) the cells responding to IL-6 during infection in the Peyer s patch, mesenteric lymph node, and spleen. These data will give us insight into which host cells are modulating the host response to infection. 3) Test the contribution of the IL-6 modulated cytokines to the immunopathogenesis of intestinal yersiniosis. Mice deficient in IL-6 have distinct cytokine expression profiles and many of these cytokines are critical to the resolution of disease but it is unknown how mis-regulation of these cytokines contributes to pathology. These data will explore the connection between IL-6 mediated modulation of the immune response and Yersinia virulence. Altogether, these data will give us insight into how IL-6 contributes to the pathogenesis of Yersinia infection and how immune pathologies are prevented during self limiting infections. These data may provide insight into the etiology of chronic intestinal inflammation.
Keywords: infection, role, Carnivora, Peyer s patches, Yersinia, Yersinia pestis disease, back, bacteria, cell, children, communicable disease, culture, cytokine, food, gastrointestinal disorder, immune response, immune system, immunoregulation, inflammation, insight, lead, learning, lymph node, model, pathology, plasmid, play, receptor, secretion, spleen, syndrome, thinking, virulence, water
Project start date: 2007-06-01
Project end date: 2012-05-31
1R01AI067716-01A2 (2007): $365000
ROLE OF CARDS TOXIN IN M. PNEUMONIAE ASSOCIATED ASTHMA IN MICE
Peter H Dube
University Of Texas Hlth Sci Ctr San Ant, San Antonio, Tx 78229
Abstract: Asthma is a complex disease that afflicts over 15 million Americans. Despite the apparent increase in prevalence of disease within our population, asthma is still a poorly understood disease. This is in part due to the complex mixture of genetic factors, environmental stimuli, and immune system status that impacts disease development and progression. One under appreciated and controversial factor in the etiology of asthma is the role that atypical bacterial infections, such as those caused by Mycoplasma pneumoniae, play in initiating, exacerbating and prolonging airway-related symptoms and pathologies. A major part of the confusion is the lack of reliable and relevant diagnostic methodologies and bona fide virulence determinants that directly link M. pneumoniae to asthma pathogenesis. Recently a unique M. pneumoniae toxin (CARDS TX Community Acquired Respiratory Distress Syndrome Toxin) was discovered (see Preliminary results section and Project 4) that replicates the cytokine responses, pathology, and changes in airway hyperresponsiveness observed with M. pneumoniae respiratory infections and M. pneumoniae-assocated asthma. We consider this finding a potential major breakthrough and hypothesize that CARDS TX may be responsible for acute, chronic, and exacerbation of asthma. To test this hypothesis, we will take advantage of the BALB/c-ovalbumin model of allergic asthma to test the following Specific aims 1) Determine the contribution of our newly discovered ADP ribosylating, vacuolating CARDS TX to the pathogenesis of M. pneumoniae associated allergic asthma using established murine models, 2) Investigate the role of CARDS TX in the pathogenesis of asthma associated with M. pneumoniae infection. Mice will be infected with wild type M. pneumoniae or M. pneumoniae with a null mutation in the CARDS TX gene. Pathogenesis will be evaluated in the BALB/c mouse model with and without ovalbumin-induced airway hyper-responsiveness, to elucidate the role of CARDS TX in the context of the infectious model, and 3) Investigate the activity of CARDS TX in vivo. We will refine our analysis of the impact of CARDS TX on M. pneumon/ae-mediated respiratory disease through the analysis of CARDS TX-induced gene expression, localization/co-localization, and biochemical activity in vivo using the BALB/c mouse model with and without ovalbumin-induced airway hyper-responsiveness. The studies outlined in this project provide an asthma experimental model to correlate with clinical findings from Project 3; experiments using chronic models of infection described in Project 1; mutants, reagents and biochemical and molecular observations developed in Project 4; and Pathology Core B expertise
Keywords: Accounting; Acute; Airway Hyper-responsiveness; Allergic asthma; American; Animal Model; Animal Models and Related Studies; Animals; Assay; Asthma; BALB/c; Bacterial Infections; Bioassay; Biochemical; Biologic Assays; Biological Assay; Bronchial Asthma; Causality; Cells; Chronic; Chronic Disease; Chronic Illness; Clinical; Collaborations; Community Acquired Respiratory Distress Syndrome Toxin; Complex; Complex Mixtures; Confusion; Confusional State; Control Animal; Development; Diagnostic; Disease; Disorder; Eaton Agent; Eaton Liu agent; Economics; Ensure; Environmental Factor; Environmental Risk Factor; Etiology; Experimental Designs; Experimental Models; Experimental Models, Other; Exposure to; Extrinsic asthma; Gene Expression; Genes; Genetic; Goals; Histopathology; Human; Human, General; IMPHENO; Immune; Immune response; Immune system; Immunophenotyping; Inbred BALB C Mice; Individual; Infection; Intoxication; Investigators; Length; Link; Lung; Lung diseases; M. pneumoniae; Mammals, Mice; Mammals, Rodents; Man (Taxonomy); Man, Modern; Mediating; Mental Confusion; Method LOINC Axis 6; Methodology; Mice; Mice, Inbred BALB C; Modeling; Models, Experimental; Molecular; Molecular Genetic; Molecular Genetics; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Mouse, BALB C; Murine; Mus; Mycoplasma pneumoniae; Ovalbumin; Pathogenesis; Pathogenicity Factors; Pathology; Phenotype; Physiologic; Physiological; Play; Pneumonia; Pneumonitis; Population; Prevalence; Protocol; Protocols documentation; Pulmonary Diseases; Pulmonary Disorder; Pulmonary Inflammation; QOL; Quality of life; Reagent; Relative; Relative (related person); Research Personnel; Research Specimen; Researchers; Respiratory Disease; Respiratory Disorder; Respiratory Infections; Respiratory System Disease; Respiratory System Disorder; Respiratory System, Lung; Respiratory Tract Infections; Rodent; Rodent Model; Rodentia; Rodentias; Role; Sampling; Scientist; Specimen; Stimulus; Subtyping, Immunologic; Subtypings, Immunologic; Symptoms; Testing; Therapeutic Intervention; Toxin; Virulence; Virulence Factors; Work; ing; airway hyper-reactivity; airway hyperreactivity; airway hyperresponsiveness; airway remodeling; atopic asthma; bacterial disease; body system, allergic/immunologic; chronic disease/disorder; chronic disorder; cytokine; disease causation; disease etiology; disease/disorder; disease/disorder etiology; disorder etiology; environmental risk; experiment; experimental research; experimental study; extrinsic allergic asthma; host response; immunophenotype; immunoresponse; in vivo; insight; intervention therapy; lung disorder; model organism; mouse model; mutant; novel; null mutation; organ system, allergic/immunologic; pulmonary; research study; response; social role
Budget start date: 1-AUG-2010
Budget end date: 31-JUL-2011
5U19AI070412-05_0007 (2010): $188707
3U19AI070412-04S1_0007 (2009): $52008
5U19AI070412-04_0007 (2009): $190613