| Autor: |
Scordo JM; Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.; Texas Biomedical Research Institute, San Antonio, TX, 78229, USA., Olmo-Fontánez AM; Texas Biomedical Research Institute, San Antonio, TX, 78229, USA., Kelley HV; Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.; Texas Biomedical Research Institute, San Antonio, TX, 78229, USA., Sidiki S; Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA., Arcos J; Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA., Akhter A; Texas Biomedical Research Institute, San Antonio, TX, 78229, USA., Wewers MD; Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine Division, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA., Torrelles JB; Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA. jtorrelles@txbiomed.org.; Texas Biomedical Research Institute, San Antonio, TX, 78229, USA. jtorrelles@txbiomed.org. |
| Abstrakt: |
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. |
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