The human lung mucosa drives differential Mycobacterium tuberculosis infection outcome in the alveolar epithelium
| Autor: | Mark D. Wewers, Sabeen Sidiki, Holden V. Kelley, Jesus Arcos, Angélica Olmo-Fontánez, Julia M. Scordo, Anwari Akhter, Jordi B. Torrelles |
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| Rok vydání: | 2019 |
| Předmět: |
Cytotoxicity
Immunologic DNA Replication DNA Bacterial 0301 basic medicine Phagocyte Alveolar Epithelium Phagocytosis Immunology Apoptosis Inflammation Respiratory Mucosa alveolar epithelial cells Article Microbiology 03 medical and health sciences 0302 clinical medicine Immune system Cell Adhesion medicine Humans Immunology and Allergy Macrophage Cell adhesion Lung Tuberculosis Pulmonary A549 cell Chemistry digestive oral and skin physiology Epithelial Cells Mycobacterium tuberculosis Immunity Innate 3. Good health Pulmonary Alveoli 030104 developmental biology medicine.anatomical_structure A549 Cells medicine.symptom human alveolar lining fluid 030215 immunology |
| Zdroj: | Mucosal immunology |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/s41385-019-0156-2 |
| Popis: | Mycobacterium tuberculosis (M.tb) is deposited into the alveolus where it first encounters the alveolar lining fluid (ALF) prior contacts host cells. We demonstrated that M.tb-exposure to human ALF alters its cell surface, driving better M.tb infection control by professional phagocytes. Contrary to these findings, our results with non-professional phagocytes alveolar epithelial cells (ATs) define two distinct subsets of human ALFs; where M.tb exposure to Low (L)-ALF or High(H)-ALF results in low or high intracellular bacterial growth rates in ATs, respectively. H-ALF exposed-M.tb growth within ATs was independent of M.tb-uptake, M.tb-trafficking, and M.tb-infection induced cytotoxicity; however, it was associated with enhanced bacterial replication within LAMP-1+/ABCA1+ compartments. H-ALF exposed-M.tb infection of ATs decreased AT immune mediator production, decreased AT surface adhesion expression, and downregulated macrophage inflammatory responses. Composition analysis of H-ALF vs. L-ALF showed H-ALF with higher protein tyrosine nitration and less functional ALF-innate proteins important in M.tb pathogenesis. Replenishment of H-ALF with functional ALF-innate proteins reversed the H-ALF-M.tb growth rate to the levels observed for L-ALF-M.tb. These results indicate that dysfunctionality of innate proteins in the H-ALF phenotype promotes M.tb replication within ATs, while limiting inflammation and phagocyte activation, thus potentiating ATs as a reservoir for M.tb replication and survival. |
| Databáze: | OpenAIRE |
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