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The human lung mucosa drives differential Mycobacterium tuberculosis infection outcome in the alveolar epithelium.

Abstract：

: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.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Scordo JM,Olmo-Fontánez AM,Kelley HV,Sidiki S,Arcos J,Akhter A,Wewers MD,Torrelles JB

doi

10.1038/s41385-019-0156-2

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

795-804

issue

3

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-019-0156-2

journal_volume

12

pub_type

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