Document text
Principal Investigator: Thomas Parks Remcho
Organization: TULANE UNIVERSITY OF LOUISIANA
Fiscal Year: 2024
Award: $53,167
Funding agency: National Heart Lung and Blood Institute
Pneumonia is the leading killer of children globally and a significant cause of morbidity and
mortality in the US. Pneumonias due to drug-resistant Enterobacteriaceae are an emerging
problem. Our lab has shown that lung tissue resident memory (TRM) cells, consisting of Th17
and Th1 cells, provide profound protection against hyper-virulent K. pneumoniae strains.
Interestingly, these cells must signal through lung fibroblasts to provide protection as deletion of
IL-17RC in Dermo1+ or Col1a2+ cells compromises TRM efficacy. Based on our prior work and
preliminary results, we hypothesize that vaccine-induced Th17 cells signal lung fibroblasts to
secrete the chemokines responsible for recruiting macrophages to the interstitial compartment
of the lung and improve the ability of local macrophages to clear K. pneumoniae. To test this,
we propose the following aims: Aim 1: Evaluate the response of lung fibroblasts to Th17-
associated cytokines (IL17A, IL17F, TNF) and examine the chemotactic and phenotypic impact
fibroblast-derived signals have on several myeloid/monocyte populations. Aim 2: Evaluate the
dependence of bacterial clearance on vaccine-elicited host TRM populations, fibroblast
signaling, and myeloid cell recruitment and modification in vivo. We propose the macrophage
population recruited via fibroblast signaling is (a) the direct downstream result of establishing
TRM cells, (b) key to vaccine efficacy, and (c) phenotypically and locationally well-suited to
clearance of the pathogen.
Terms: <(TNF)-α><0-11 years old><4q Chemokine><ATAC><Alveolar Lavage Fluids><Assay><Bacteria><Bacterial Pneumonia><Binding><Bioassay><Biological Assay><Biology><Blood monocyte><Body Tissues><Bone Marrow><Bone Marrow Reticuloendothelial System><Bone-Derived Transforming Growth Factor><Bronchial Lavage Fluid><Bronchoalveolar Lavage Fluid><C-C Chemokines><C-X-C Chemokines><CC Chemokines><CD11b><CD11c><CR3A><CTLA-8><CTLA-8 Gene><CTLA8><CTLA8 Gene><CXC Chemokines><Cachectin><Cell Body><Cell Communication and Signaling><Cell Function><Cell Isolation><Cell Line><Cell Locomotion><Cell Migration><Cell Movement><Cell Physiology><Cell Process><Cell Segregation><Cell Separation><Cell Separation Technology><Cell Signaling><CellLine><Cells><Cellular Function><Cellular Migration><Cellular Motility><Cellular Physiology><Cellular Process><Chemotactic Cytokines><Child><Child Youth><Children (0-21)><Coliform Bacilli><Communication><Complement><Complement Proteins><Cramp><Cytotoxic T-Lymphocyte-Associated Antigen 8><Cytotoxic T-Lymphocyte-Associated Antigen 8 Gene><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8 Gene><Data><Dependence><Development><Diagnosis><Drug resistance><Effector Cell><Enteric Bacteria><Enterobacteria><Enterobacteriaceae><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Epithelial Cells><Exposure to><Fibroblasts><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Foundations><Gene Transcription><Generations><Genetic Transcription><Goals><HIF 1 alpha><HIF-1alpha><HIF1-Alpha><HIF1A><HIF1A gene><HIF1α><Homolog of Drosophila TOLL><Homologous Chemotactic Cytokines><Human><IL-17><IL-17 Gene><IL-17A><IL-17A Gene><IL17><IL17 Protein><IL17 gene><IL17A><IL17A Gene><ITGAM><ITGAM gene><ITGAX><ITGAX gene><Immune><Immunes><Immunology><In Vitro><Intercrines><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8)><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8) Gene><Interleukin 17 Precursor><Interleukin 17 Precursor Gene><Interleukin-17><Intracellular Communication and Signaling><K pneumoniae><K. pneumoniae><Klebsiella pneumoniae><LPTN><Location><Lung><Lung Lavage Fluid><Lung Parenchyma><Lung Respiratory System><Lung Tissue><MAC1A><MO1A><MOP1><Macrophage><Macrophage-Derived TNF><Marrow monocyte><Measures><Memory><Methods><Mice><Mice Mammals><Milk Growth Factor><Modern Man><Modification><Molecular Interaction><Monocyte-Derived TNF><Morbidity><Morbidity - disease rate><Mucosa><Mucosal Tissue><Mucous Membrane><Murine><Mus><Muscle Cramp><Muscular Cramp><Myelogenous><Myeloid><Myeloid Cells><Mφ><Nasal><Nasal Passages Nose><Neutrophil Infiltration><Neutrophil Recruitment><Neutrophilic Infiltrate><Nose><Phenotype><Physicians><Platelet Transforming Growth Factor><Pneumonia><Population><Pulmonary Body System><Pulmonary Organ System><RNA Expression><Receptor Protein><Regulation><Research><Respiratory System><Respiratory System, Nose, Nasal Passages><Respiratory Tracts><Respiratory tract structure><Role><SCM-1><SCM-1a><SCM1><SCYC1><SIS cytokines><Scientist><Signal Transduction><Signal Transduction Systems><Signaling><Sorting><Strains Cell Lines><Structure of parenchyma of lung><Subcellular Process><Surface><TGF B><TGF-beta><TGF-β><TGFbeta><TGFβ><TLR4><TLR4 gene><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Testing><Th-1 Cell><Th1 Cells><Tissues><Toll Homologue><Training><Transcription><Transforming Growth Factor beta><Transforming Growth Factor-Beta Family Gene><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Type 1 Helper Cell><Vaccines><Validation><Work><XCL1><XCL1 gene><alpha-Chemokines><anti-microbial><antimicrobial><bacteria pneumonia><bactericidal><bactericide><beta-Chemokines><biological signal transduction><bronchial epithelium><cell motility><cell sorting><chemoattractant cytokine><chemokine><chemokine therapy><complementation><cultured cell line><cytokine><developmental><drug resistant><epigenetically><experiment><experimental research><experimental study><experiments><flow cytophotometry><improved><in vivo><interstitial><kids><knock-down><knockdown><mRNA Stability><monocyte><mortality><pathogen><pulmonary><receptor><recruit><residence><residential building><residential site><resilience><resilient><resistance to Drug><resistant to Drug><response><social role><toll-like receptor 4><vaccine efficacy><validations><youngster><β-Chemokines>