A Neoglycoconjugate Containing the Human Milk Sugar LNFPIII Drives Anti-Inflammatory Activation of Antigen Presenting Cells in a CD14 Dependent Pathway

PloS One
Smanla TundupDonald Harn

Abstract

The milk pentasaccharide LNFPIII has therapeutic action for metabolic and autoimmune diseases and prolongs transplant survival in mice when presented as a neoglycoconjugate. Within LNFPIII is the Lewisx trisaccharide, expressed by many helminth parasites. In humans, LNFPIII is found in human milk and also known as stage-specific embryonic antigen-1. LNFPIII-NGC drives alternative activation of macrophages and dendritic cells via NFκB activation in a TLR4 dependent mechanism. However, the connection between LNFPIII-NGC activation of APCs, TLR4 signaling and subsequent MAP kinase signaling leading to anti-inflammatory activation of APCs remains unknown. In this study we determined that the innate receptor CD14 was essential for LNFPIII-NGC induction of both ERK and NFkB activation in APCs. Induction of ERK activation by LNFPIII-NGC was completely dependent on CD14/TLR4-Ras-Raf1/TPL2-MEK axis in bone marrow derived dendritic cells (BMDCs). In addition, LNFPIII-NGC preferentially induced the production of Th2 "favoring" chemokines CCL22 and matrix metalloprotease protein-9 in a CD14 dependent manner in BMDCs. In contrast, LNFPIII-NGC induces significantly lower levels of Th1 "favoring" chemokines, MIP1α, MIP1β and MIP-2 compared to...Continue Reading

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Citations

Nov 23, 2017·Frontiers in Microbiology·Zhenyu WuXi Sun
Oct 1, 2020·International Journal of Environmental Research and Public Health·Ryan S MoteNikolay M Filipov
Nov 10, 2020·Pharmacology & Therapeutics·Brandon DickeyAshok K Shetty
May 1, 2021·International Journal of Molecular Sciences·Svetlana KononovaStanislav Sitkin
Jun 18, 2021·Life Sciences·Saurabh ChatterjeeRatanesh Seth

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Datasets Mentioned

BETA
GMCSF

Methods Mentioned

BETA
nuclear translocation
Flow Cytometry
ELISA
electrophoresis
Assay
GTPase
pull-down
pulled down

Software Mentioned

Prism
GraphPad

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