Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response

Melkebeek, Vesna; Rasschaert, Kristien; Bellot, Philippe; Tilleman, Kelly; Favoreel, Herman; Deforce, Dieter; Geest, Bruno G. De; Goddeeris, Bruno; Cox, Eric

doi:10.1038/mi.2012.37

Cited by 42 publications

(53 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD13 can mediate internalization of large particles (4 mm), which strongly argues in favor of phagocytosis and excludes other forms of internalization. This is of particular importance, as CD13 has been implicated in the endocytosis of coronavirus [25,[50][51][52], proteins [53], targeted peptides [54], or antibodies [25,53] in several cells types. The reported forms of CD13-mediated endocytosis are caveolae-mediated endocytosis [25,55] and clathrinmediated endocytosis [50,56].…”

Section: Discussionmentioning

confidence: 99%

CD13 mediates phagocytosis in human monocytic cells

Licona‐Limón

Garay-Canales

Muñoz-Paleta

et al. 2015

Journal of Leukocyte Biology

View full text Add to dashboard Cite

CD13 is a membrane-bound ectopeptidase, highly expressed on monocytes, macrophages, and dendritic cells. CD13 is involved in diverse functions, including degradation of peptide mediators, cellular adhesion, migration, viral endocytosis, signaling, and positive modulation of phagocytosis mediated by FcγRs and other phagocytic receptors. In this work, we explored whether besides acting as an accessory receptor, CD13 by itself is a primary phagocytic receptor. We found that hCD13 mediates efficient phagocytosis of large particles (erythrocytes) modified so as to interact with the cell only through CD13 in human macrophages and THP-1 monocytic cells. The extent of this phagocytosis is comparable with the phagocytosis mediated through the canonical phagocytic receptor FcγRI. Furthermore, we demonstrated that hCD13 expression in the nonphagocytic cell line HEK293 is sufficient to enable these cells to internalize particles bound through hCD13. CD13-mediated phagocytosis is independent of other phagocytic receptors, as it occurs in the absence of FcγRs, CR3, and most phagocytic receptors. Phagocytosis through CD13 is independent of its enzymatic activity but is dependent on actin rearrangement and activation of PI3K and is partially dependent on Syk activation. Moreover, the cross-linking of CD13 with antibodies rapidly induced pSyk in human macrophages. Finally, we observed that antibody-mediated cross-linking of hCD13, expressed in the murine macrophage-like J774 cell line, induces production of ROS. These results demonstrate that CD13 is a fully competent phagocytic receptor capable of mediating internalization of large particles.

show abstract

Section: Discussionmentioning

confidence: 99%

CD13 mediates phagocytosis in human monocytic cells

Licona‐Limón

Garay-Canales

Muñoz-Paleta

et al. 2015

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…It is most likely that the context of this sequence on the different receptors is responsible for the binding specificities of the F4 variants. In contrast, the F4 aminopeptidase N receptor is glycosylated and biochemical evidence indicated that sialic acid was needed for binding (160), whereas transcription levels or single nucleotide polymorphisms (SNPs) could not explain the various binding profiles of three F4 variants (161). Recent studies characterized some of the porcine intestinal carbohydrate receptor moieties interacting with the F4 fimbriae (162).…”

Section: Adhesins and Host Receptorsmentioning

confidence: 99%

Animal EnterotoxigenicEscherichia coli

2016

View full text Add to dashboard Cite

Enterotoxigenic Escherichia coli (ETEC) is the most common cause of E. coli diarrhea in farm animals. ETEC are characterized by the ability to produce two types of virulence factors; adhesins that promote binding to specific enterocyte receptors for intestinal colonization and enterotoxins responsible for fluid secretion. The best-characterized adhesins are expressed in the context of fimbriae, such as the F4 (also designated K88), F5 (K99), F6 (987P), F17 and F18 fimbriae. Once established in the animal small intestine, ETEC produces enterotoxin(s) that lead to diarrhea. The enterotoxins belong to two major classes; heat-labile toxin that consist of one active and five binding subunits (LT), and heat-stable toxins that are small polypeptides (STa, STb, and EAST1). This chapter describes the disease and pathogenesis of animal ETEC, the corresponding virulence genes and protein products of these bacteria, their regulation and targets in animal hosts, as well as mechanisms of action. Furthermore, vaccines, inhibitors, probiotics and the identification of potential new targets identified by genomics are presented in the context of animal ETEC.

show abstract

“…Among the three different antigenic variants (F4ab, F4ac, and F4ad) of F4 fimbriae, F4ac is the most prevalent [4], [5]. ETEC having F4ac fimbriae inducing severe diarrhoea is dependent on the presence of the specific receptors for F4ac (F4acR) [6], which is encoded by the responsible gene [7]. To date, the candidate genes of F4acR having been investigated in several specific pig populations by association study between genetic markers with in vitro F4ac adhesion phenotypes include: mucin 4 ( MUC4 ) [8], MUC13 [7], [9], MUC20 [10] and integrin beta-5 ( ITGB5 ) [11].…”

Section: Introductionmentioning

confidence: 99%

Gene Silencing of Porcine MUC13 and ITGB5: Candidate Genes towards Escherichia coli F4ac Adhesion

Zhou

Liu

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

BackgroundIntegrin beta-5 (ITGB5) and mucin 13 (MUC13) genes are highly expressed on the apical surface of intestinal epithelia and are thought to be candidate genes for controlling the expression of the receptor for enterotoxigenic Escherichia coli (ETEC) F4ac. Human MUC13 protein has an expected role in protecting intestinal mucosal surfaces and porcine ITGB5 is a newly identified potential receptor for ETEC F4ac.Methodology/Principal FindingsTo test the hypothesis that ITGB5 and MUC13 both play key roles in protection of the intestinal mucosa against pathogenic bacterium, porcine intestinal epithelial cells (IPEC-J2) were transfected with ITGB5-targeting, MUC13-targeting or negative control small interfering RNA (siRNA), respectively. Firstly, we measured mRNA expression levels of mucin genes (MUC4, MUC20), pro-inflammatory genes (IL8, IL1A, IL6, CXCL2), anti-inflammatory mediator SLPI, and PLAU after RNAi treatments with and without ETEC infection. Secondly, we compared the adhesions of ETEC to the pre- and post-knockdown IPEC-J2 cells of ITGB5 and MUC13, respectively. We found that ITGB5 and MUC13 knockdown both had small but significant effects in attenuating the inflammation induced by ETEC infection, and both increased bacterial adhesion in response to F4ac ETEC exposure.Conclusions/SignificanceOur current study first reported that ITGB5 and MUC13 are important adhesion molecules of mucosal epithelial signaling in response to Escherichia coli in pigs. These data suggest that both ITGB5 and MUC13 play key roles in defending the attachment and adhesion of ETEC to porcine jejunal cells and in maintaining epithelial barrier and immunity function.

show abstract

Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response

Cited by 42 publications

References 35 publications

CD13 mediates phagocytosis in human monocytic cells

CD13 mediates phagocytosis in human monocytic cells

Animal EnterotoxigenicEscherichia coli

Gene Silencing of Porcine MUC13 and ITGB5: Candidate Genes towards Escherichia coli F4ac Adhesion

Contact Info

Product

Resources

About