Abstract
BackgroundThe small intestine is a specialized compartment were close interactions take place between host, microbes, food antigens and dietary fatty acids. Dietary fats get absorbed by epithelial cells and processed into a range of lipoprotein particles after which they are basolaterally secreted and collected in the lymphatics. In contrast to the colon, the small intestine is covered only by a thin mucus coat that allows for intimate interactions between host-cells and microbes. Lipoproteins have long been recognized as protective factors in infectious diseases via the neutralization of bacterial toxins like lipopolysaccharides. Much less attention has been given to the potential role of lipoproteins as factors contributing to the maintenance of small intestinal immune homeostasis via modulating bacteria-induced immune responses.ResultsLipoproteins VLDL, LDL and HDL were found to neutralize TLR responses towards specific TLR-ligands or a selection of gram-negative and gram-positive bacteria. Attenuation of TLR2 activity was acute and only slightly improved by longer pre-incubation times of ligands and lipoproteins with no differences between bacterial-lipopeptides or bacteria. In contrast, attenuation of TLR4 responses was only observed after extensive preincubation of lipoproteins and LPS. Preincubation of bacteria and lipoproteins led only to a modest attenuation of TLR4 activity. Moreover, compared to TLR2, TLR4 activity could only be attenuated by lipoproteins over a small ligand dose range.ConclusionsThese results demonstrate the ability of lipoproteins VLDL, LDL and HDL to inhibit TLR responses towards bacterial-ligands and bacteria. Presence of lipoproteins was found to modulate the MAMP-induced cytokine release by primary human monocytes measured as changes in the release of IL-6, TNFα, GM-CSF and IFNγ. Using TLR2 and TLR4-reporter cells, lipoproteins were found to inhibit TLR responses with differences in affinity and kinetics. These data establish a role for lipoproteins as immunoregulatory molecules, attenuating TLR-responses and thereby positively contributing to mucosal homeostasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0180-x) contains supplementary material, which is available to authorized users.
Highlights
The small intestine is a specialized compartment were close interactions take place between host, microbes, food antigens and dietary fatty acids
To investigate whether serum lipoproteins are able to modify cellular responses to bacteria, we challenged human primary monocytes with the gram-positive bacteria Bifidobacterium breve and Lactobacillus salivarius, the gram-negative bacteria Escherichia coli and Salmonella typhimurium and the TLR2 specific ligand FSL-1 and TLR4 specific ligand LPS in the presence of intact human serum (HS) or human serum depleted for lipoproteins (HSdelip) and measured cytokine release (Fig. 1 and Additional file 1)
Data indicates that TNFα, IL-6, GM-CSF and IFNγ release were affected by the presence of serum lipoproteins depending on bacterial strain or Toll-like receptor (TLR)-ligand
Summary
The small intestine is a specialized compartment were close interactions take place between host, microbes, food antigens and dietary fatty acids. Much less attention has been given to the potential role of lipoproteins as factors contributing to the maintenance of small intestinal immune homeostasis via modulating bacteria-induced immune responses. It is well known that infection and inflammation induce an acute-phase response, leading to changes in plasma lipids and lipoprotein metabolism which in turn add to the inflammatory cycle potentially leading to atherosclerosis [1]. It has long van Bergenhenegouwen et al BMC Immunology (2016) 17:42. The data suggests that lipoprotein deposits on bacterial surfaces modulate hostmicrobe interactions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
