A Duffy Binding–Like Domain Is Involved in the NKp30‐Mediated Recognition of<i>Plasmodium</i><i>falciparum</i>–Parasitized Erythrocytes by Natural Killer Cells

Mavoungou, Elie; Held, Jana; Mewono, Ludovic; Kremsner, Peter G.

doi:10.1086/515579

Cited by 80 publications

(81 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several ligands have been identified for NKp30 (11)(12)(13)(14)(15)(16). Although the physiological significance of these ligands remains to be investigated, the ligands do not share any sequence homology nor a predicted structural fold.…”

Section: Resultsmentioning

confidence: 99%

Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site

Joyce

Tran

Zhuravleva

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Natural killer (NK) cells are a group of innate immune cells that carry out continuous surveillance for the presence of virally infected or cancerous cells. The natural cytotoxicity receptor (NCR) NKp30 is critical for the elimination of a large group of tumor cell types. Although several ligands have been proposed for NKp30, the lack of a conserved structural feature among these ligands and their uncertain physiological relevance has contributed to confusion in the field and hampered a full understanding of the receptor. To gain insights into NKp30 ligand recognition, we have determined the crystal structure of the extracellular domain of human NKp30. The structure displays an I-type Ig-like fold structurally distinct from the other natural cytotoxicity receptors NKp44 and NKp46. Using cytolytic killing assays against a range of tumor cell lines and subsequent peptide epitope mapping of a NKp30 blocking antibody, we have identified a critical ligand binding region on NKp30 involving its F strand. Using different solution binding studies, we show that the N-terminal domain of B7-H6 is sufficient for NKp30 recognition. Mutations on NKp30 further confirm that residues in the vicinity of the F strand, including part of the C strand and the CD loop, affect binding to B7-H6. The structural comparison of NKp30 with CD28 family receptor and ligand complexes also supports the identified ligand binding site. This study provides insights into NKp30 ligand recognition and a framework for a potential family of unidentified ligands.

show abstract

Section: Resultsmentioning

confidence: 99%

Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site

Joyce

Tran

Zhuravleva

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Additionally, various parasite proteins can bind to host receptors directly and modulate host responses; for example, circumsporozoite protein (CSP) was reported to interfere with the nuclear translocation of NF-κB (30), and proteins with Duffy binding-like (DBL) domains such as the P. falciparum erythrocyte membrane protein 1 (PfEMP1) or erythrocyte binding ligand (EBL) are able to bind to host cells expressing CD36, ICAM1, and/or Duffy antigen receptor for chemokine (DARC) and to trigger (or suppress) the host inflammatory response (31,32). Variations in these molecules or others in the parasite genome can influence the host response and disease outcomes.…”

mentioning

confidence: 99%

Strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality

Tian

Xiao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

143

View full text Add to dashboard Cite

Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors, and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within RBCs, thereby hiding themselves from direct contact and recognition by host immune cells. Host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been elusive. Here we investigated mouse genome-wide transcriptional responses to infections with two strains of Plasmodium yoelii (N67 and N67C) and discovered differences in innate response pathways corresponding to strain-specific disease phenotypes. Using in vitro RNAi-based gene knockdown and KO mice, we demonstrated that a strong type I IFN (IFN-I) response triggered by RNA polymerase III and melanoma differentiation-associated protein 5, not Toll-like receptors (TLRs), binding of parasite DNA/RNA contributed to a decline of parasitemia in N67-infected mice. We showed that conventional dendritic cells were the major sources of early IFN-I, and that surface expression of phosphatidylserine on infected RBCs might promote their phagocytic uptake, leading to the release of parasite ligands and the IFN-I response in N67 infection. In contrast, an elevated inflammatory response mediated by CD14/TLR and p38 signaling played a role in disease severity and early host death in N67C-infected mice. In addition to identifying cytosolic DNA/RNA sensors and signaling pathways previously unrecognized in malaria infection, our study demonstrates the importance of parasite genetic backgrounds in malaria pathology and provides important information for studying human malaria pathogenesis.

show abstract

“…Human immunodeficiency virus, vaccinia virus, and herpes simplex virus have also been shown to upregulate the expression of cellular NCR ligands in infected cells (13,14,62). The Plasmodium falciparum erythrocyte membrane protein 1 is involved in the NCR-mediated NK cell attack against infected erythrocytes (36). Furthermore, NKp46 recognizes cells infected with mycobacteria (22,61), and NKp44 was recently reported to directly bind to the surfaces of mycobacteria and other bacteria (21).…”

mentioning

confidence: 99%

Activation of Natural Killer Cells by Newcastle Disease Virus Hemagglutinin-Neuraminidase

Jarahian¹,

Watzl

Fournier³

et al. 2009

J Virol

153

160

View full text Add to dashboard Cite

A Duffy Binding–Like Domain Is Involved in the NKp30‐Mediated Recognition ofPlasmodiumfalciparum–Parasitized Erythrocytes by Natural Killer Cells

Cited by 80 publications

References 35 publications

Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site

Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site

Strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality

Activation of Natural Killer Cells by Newcastle Disease Virus Hemagglutinin-Neuraminidase

Contact Info

Product

Resources

About