A Novel Lipopolysaccharide Recognition Mechanism Mediated by Internalization in Teleost Macrophages

Abstract

Macrophages in teleosts are less sensitive to lipopolysaccharide (LPS) compared to mammals. The functional equivalent of the mammalian LPS surface receptor in teleost macrophages for the pro-inflammatory response is either non-existent or replaced by negative regulation. LPS signaling in teleost macrophages remains unclear. Here, we found a scavenger receptor class B 2a (PaSRB2a) that played a crucial role in LPS signaling in teleost macrophages. The internalization of LPS and subsequent pro-inflammatory responses in macrophages were mediated by PaSRB2a, which is a novel isoform of the mammalian SRB2 gene. LPS internalization by PaSRB2a is dependent on its C-terminal intracellular domain. Following LPS internalization, it interacts with the ayu intracellular receptors nucleotide-binding oligomerization domain protein 1 (PaNOD1) and PaNOD2. Moreover, LPS pre-stimulation with sub-threshold concentrations reduced the effect of secondary LPS treatment on pro-inflammatory responses that were mediated by PaSRB2a. The pro-inflammatory responses in LPS-treated ayu were down-regulated upon PaSRB2a knockdown by lentivirus siRNA delivery. In grass carp and spotted green pufferfish, SRB2a also mediated LPS internalization and pro-inflammatory responses. Our work identifies a novel LPS signaling pathway in teleosts that differs from those in mammals, and contributes to our understanding of the evolution of pathogen recognition in vertebrates.

CXCR4s in Teleosts: Two Paralogous Chemokine Receptors and Their Roles in Hematopoietic Stem/Progenitor Cell Homeostasis

“…Hence, we found specific LPS-mobilized HSPCs marked by CXCR4a, suggesting that teleosts produce bacterial infectionderived HSPCs. In our previous work, we identified SRB2a as the late-phase allergic skin reaction in teleost macrophages, including those from ayu (52). In this study, we found that both We further found that CXCR4b preferred to interact with SDF-1, which is the sole endogenous chemokine ligand for the CXCR4 of mammalian HSPCs (29).…”

Paralogues From the Expanded Tlr11 Gene Family in Mudskipper (Boleophthalmus pectinirostris) Are Under Positive Selection and Respond Differently to LPS/Poly(I:C) Challenge

“…Recently, study in miiuy croaker ( Miichthys miiuy ) showed that NOD1 can identify LPS and activate the NF-κB signal pathway by recruiting RIPK2 and then promoting the expression of inflammatory cytokines to induce the resistance of organism against bacterial infection (59). Another study further demonstrated that scavenger receptor class B 2a (SRB2a), a novel isoform of the mammalian SRB2 gene, mediates LPS internalization for interaction with NOD1 and NOD2 to initiate NF-κB in teleost macrophages (60). The results from the present study suggest that BpTlr21 may be involved in immune response to bacterial infection in B. pectinirostris , and further studies should be focused on whether the stimulatory effects of LPS on Bp tlr21 was mediated by SRB2a and NOD in B. pectinirostris .…”

Porphyromonas gulae lipopolysaccharide elicits inflammatory responses through toll‐like receptor 2 and 4 in human gingivalis epithelial cells

“…gulae LPS recruits TLR2 and TLR4 as upstream actors for signalling pathways, leading to enhanced inflammatory responses in Ca9‐22 cells. Additionally, Aeromonas hydrophila LPS and Vibrio anguillarum LPS, extracted by the same method as us, were induced inflammatory responses, while TLR2 did not activated (Lu, Ning, Liu, Nie, & Chen, 2018). On the other hand, previous reports noted that the expression was upregulated following A .…”