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Differential Host Pro-Inflammatory Response to Mycobacterial Cell Wall Lipids Regulated by the Mce1 Operon.


ABSTRACT: The cell wall of wild-type (WT) Mycobacterium tuberculosis (Mtb), an etiologic agent of tuberculosis (TB) and a Mtb strain disrupted in a 13-gene operon mce1 (?mce1) varies by more than 400 lipid species. Here, we examined Mtb lipid-induced response in murine macrophage, as well as in human T-cell subpopulations in order to gain an insight into how changes in cell wall lipid composition may modulate host immune response. Relative to WT Mtb cell wall lipids, the non-polar lipid extracts from ?mce1 enhanced the mRNA expression of lipid-sense nuclear receptors TR4 and PPAR-? and dampened the macrophage expression of genes encoding TNF-?, IL-6, and IL-1?. Relative to untreated control, WT lipid-pre-stimulated macrophages from healthy individuals induced a higher level of CD4-CD8- double negative T-cells (DN T-cells) producing TNF-?. Conversely, compared to WT, stimulation with ?mce1 lipids induced higher mean fluorescence intensity (MFI) in IL-10-producing DN T cells. Mononuclear cells from TB patients stimulated with WT Mtb lipids induced an increased production of TNF-? by CD8+ lymphocytes. Taken together, these observations suggest that changes in mce1 operon expression during a course of infection may serve as a strategy by Mtb to evade the host pro-inflammatory responses.

SUBMITTER: Petrilli JD 

PROVIDER: S-EPMC7461851 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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