Cd14 SNPs regulate the innate immune response

Abstract

CD14 is a monocytic differentiation antigen that regulates innate immune responses to pathogens. Here, we show that murine Cd14 SNPs regulate the length of Cd14 mRNA and CD14 protein translation efficiency, and consequently the basal level of soluble CD14 (sCD14) and type I IFN production by murine macrophages. This has substantial downstream consequences for the innate immune response; the level of expression of at least 40 IFN-responsive murine genes was altered by this mechanism. We also observed that there was substantial variation in the length of human CD14 mRNAs and in their translation efficiency. sCD14 increased cytokine production by human dendritic cells (DCs), and sCD14-primed DCs augmented human CD4 T cell proliferation. These findings may provide a mechanism for exploring the complex relationship between CD14 SNPs, serum sCD14 levels, and susceptibility to human infectious and allergic diseases.

CD14 is associated with biliary stricture formation

“…Although local CD14 expression was unaffected, we identified two alternative downstream mechanisms through which TT allele carriers are protected against Gram‐negative colonization of the biliary tree. The T allele of the CD14 ‐260C>T variant was previously reported to be associated with an enhanced innate immune response . In agreement with this finding, we observed a significant up‐regulation of both IL‐8 and IL‐12p40 in mutated TT carriers after LPS stimulation in healthy whole‐blood control samples.…”

Variability of innate immune system genes in Native American populations—relationship with history and epidemiology

“…Its presence in macrophages depends on tissue type and state of activation (Geijtenbeek et al, 2000). Cluster of differentiation 14 (CD14) is a monocytic differentiation antigen that regulates innate immune responses to pathogens, acting as a co-receptor for TLR4 (Liu et al, 2012). Complement receptor (CR1) is a complement regulator that has three binding sites for C4b and two for C3b.…”

“…It can also bind C1q and MBL (mannose binding lectin) and, thus, might play a role in the complement-independent removal and phagocytosis of particles coated by these proteins (Ghiran et al, 2000). Cluster of differentiation 14 (CD14) is a monocytic differentiation antigen that regulates innate immune responses to pathogens, acting as a co-receptor for TLR4 (Liu et al, 2012). It is expressed mainly by monocyte/macrophage lineage cells and it is required for the recognition of extracellular lipopolysaccharides (LPS) and lipoteichoic acid (LTA).…”

Activation of macrophages by the ophiopogon polysaccharide liposome from the root tuber of Ophiopogon japonicus

“…CD14 is a 55-kDa glycoprotein, which is mainly expressed on mature monocytes, macrophages and activated granulocytes, and very important in the antigen presentation and intracellular signalling [27,28]. Fungal polysaccharides can activate the maturation of macrophages, stimulate the expression of major histocompatibility complex on the surface of macrophages, enhance the phagocytic activity of macrophages, and increase the production of cytokines and effector molecules [22].…”