Article
Differential Host Pro-Inflammatory Response to Mycobacterial Cell Wall Lipids Regulated by the Mce1 Operon
Registro en:
PETRILLI, Jéssica D. et al. Differential Host Pro-Inflammatory Response to Mycobacterial Cell Wall Lipids Regulated by the Mce1 Operon. Frontiers in Immunology, p. 1-10, Aug. 2020.
1664-3224
10.3389/fimmu.2020.01848
Autor
Petrilli, Jéssica D.
Müller, Igor
Araújo, Luana E
Cardoso, Thiago M.
Carvalho, Lucas Pedreira
Barros, Bruna C.
Teixeira, Maurício
Arruda, Sérgio Marcos
Riley, Lee W.
Queiroz, Adriano
Resumen
NIH FIC R25TW009338
Global Health Equity Scholarsby and in part by the
Research Program for SUS-PPSUS/BA [SUS 0027/2018].
JP was a recipient of a Ph.D. fellowship from Oswaldo
Cruz Foundation/FIOCRUZ and MT was a recipient of
a CAPES Ph.D. scholarship. AQ was a recipient of the
GHES fellowship. 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 (1mce1) 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 1mce1 enhanced the mRNA expression of lipid-sense nuclear receptors TR4 and PPAR-g and dampened the macrophage expression of genes encoding TNF-a, IL-6, and IL-1b. Relative to untreated control, WT lipid-pre-stimulatedmacrophages fromhealthy individuals induced a higher level of CD4−CD8− double negative T-cells (DN T-cells) producing TNF-a. Conversely, compared to WT, stimulation with 1mce1 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-a 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.