Structural variants of Salmonella Typhimurium lipopolysaccharide induce less dimerization of TLR4/MD-2 and reduced pro-inflammatory cytokine production in human monocytes. (July 2019)

• Record Type: Journal Article
• Authors: Aldapa-Vega, Gustavo; Moreno-Eutimio, Mario Adán; Berlanga-Taylor, Antonio J.; Jiménez-Uribe, Alexis P.; Nieto-Velazquez, Goreti; López-Ortega, Orestes; Mancilla-Herrera, Ismael; Cortés-Malagón, Enoc Mariano; Gunn, John S.; Isibasi, Armando; Wong-Baeza, Isabel; López-Macías, Constantino; Pastelin-Palacios, Rodolfo
• Is Part Of: Molecular immunology. Volume 111(2019:Jul.)
• Page Start: 43
• Page End: 52
• Publication Date: 2019-07
• Subjects: AP-1 activator protein 1 -- ERK extracellular signal regulated kinase -- IFN interferon -- IRF3 interferon regulatory factor 3 -- LPS lipopolysaccharide -- MPL monophosphoryl lipid A -- MAP kinase mitogen-activated protein kinase -- MyD88 myeloid differentiation primary response 88 -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- TLR4 toll-like receptor 4 -- TNF tumour necrosis factor -- TRIF toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β; Endotoxin -- Lipid A -- Adjuvants -- Toll-like receptor 4; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.03.003
• Languages: English
• ISSNs: 0161-5890

Abstract

Graphical abstract: Highlights: Salmonella enterica serovar Typhimurium has two modified LPS: LPS 430 and LPS 435. LPS 430 and LPS 435 induce less production of TNF-α, IL-6 and IL-1β by human monocytes. LPS 430 induces less dimerization of TLR4/MD-2 than LPS WT. LPS 430, LPS 435 and LPS WT induce similar nuclear translocation of NF-κB and IRF3. LPS 430, LPS 435 and LPS WT induce similar transcription profiles in monocytes. Abstract: Salmonella enterica serovar Typhimurium ( S. Typhimurium) changes the structure of its lipopolysaccharide (LPS) in response to the environment. The two main LPS variants found in S. Typhimurium correspond to LPS with a hepta-acylated lipid A (LPS 430) and LPS with modified phosphate groups on its lipid A (LPS 435). We have previously shown that these modified LPS have a lower capacity than wild type (WT) LPS to induce the production of pro-inflammatory cytokines in mice. Nevertheless, it is not know if LPS 430 and LPS 435 could also subvert the innate immune responses in human cells. In this study, we found that LPS 430 and LPS 435 were less efficient than WT LPS to induce the production of pro-inflammatory cytokines by human monocytes, in addition we found a decreased dimerization of the TLR4/MD-2 complex in response to LPS 430, suggesting that structurally modified LPS are sensed differently than WT LPS by this receptor; however, LPS 430 and 435 induced similar activation of the transcription factors NF-κB p65, IRF3, p38 and ERK1/2 than WT LPS. Microarray analysis of LPS 430- and LPS 435-activated monocytes revealed a gene transcription profile with differences only in the expression levels of microRNA genes compared to the profile induced by WT LPS, suggesting that the lipid A modifications present in LPS 430 and LPS 435 have a moderate effect on the activation of the human TLR4/MD-2 complex. Our results are relevant to understand LPS modulation of immune responses and this knowledge could be useful for the development of novel adjuvants and immunomodulators.