Host erythrocyte receptors for rosetting |
|
|
McQuaid F, Rowe JA. Rosetting revisited: a critical look at the evidence for host erythrocyte receptors in Plasmodium falciparum rosetting. Parasitology. 2019 28:1-43. PMID:31455446 |
NAME |
Characteristics |
STUDIES* |
COMMENTS |
ABO BLOOD GROUP ANTIGENS |
Differ based on terminal sugar: A= N-acetyl-D-galactosamine, B= D-galactose, |
Larger rosettes in parasites cultured in A, B, AB compared to O (Carlson & Wahlgren, 1992 PMID: 1402677; Udomsangpetch et al., 1993 PMID: 8447516; Barragan et al., 2000b PMID: 10768996) |
Blood group A antigen is the most well-validated host rosetting receptor. |
|
O is predominant blood group in sub-Saharan Africa |
Rosettes from group O patients are more easily disrupted by immune sera and removal of A/B antigen decreases rosette size (Barragan et al., 2000b PMID: 10768996) |
Both PfEMP1 (Vigan-Womas et al., 2012 PMID: 22807674) and RIFINs (Goel et al., 2015 PMID: 25751816) may interact with A antigen |
|
Blood group O protects against severe malaria (Rowe et al., 2007 PMID: 17959777; Fry et al., 2008 PMID: 18003641 ; Tekeste & Petros, 2010 PMID: 20939876; Rout et al., 2012 PMID: 22818742; Malaria Genomic Epidemiology Network, 2014; Ndila et al., 2018 PMID: 30033078 ; Degarege et al., 2019 PMID: 30029997) |
Parasites from group O patients have lower rosetting compared to parasites from non-O patients (Rowe et al., 1995 PMID: 7768616; Rowe et al., 2007 PMID: 1795977; Rout et al., 2012 PMID: 22818742) |
Challenging to manipulate therapeutically |
|
Blood group antigen binding site mapped to NTS-DBLa domain of PfEMP1-VarO (Vigan-Womas et al., 2012 PMID: 22807674) |
|
COMPLEMENT RECEPTOR 1 (CR1) |
Membrane glycoprotein responsible for regulating the complement system (Thielen et al., 2018 PMID: 29397262) |
Rosetting reduced in CR1 deficient erythrocytes (Rowe et al., 1997 PMID: 9230440) |
Further work needed to assess the relative importance of CR1 in rosetting isolates and potential as a therapeutic target |
|
Polymorphisms affect CR1 copy number, molecular weight and sequence (Schmidt et al., 2015 PMID: 25816986) |
Soluble CR1 and CR1 antibodies disrupt rosettes in some parasite isolates (Rowe et al., 1997 PMID: 9230440; Rowe et al., 2000 PMID: 11086071; Vigan-Womas et al., 2012 PMID: 22807674) |
Soluble recombinant CR1 has been considered for therapeutic use in humans e.g. cardiac and renal disease (Li et al., 2006 PMID: 17081086 ; Reddy et al., 2017 PMID: 27977428) |
|
RBC CR1 deficiency protects in medium-high (Cockburn et al., 2004 PMID: 14694201; Sinha et al., 2009 PMID: 19480840; Rout et al., 2011 PMID: 22818742; Panda et al., 2012 PMID: 23152904 ) but not low malaria transmission areas (Nagayasu et al., 2001 PMID: 11425154; Teeranaipong et al., 2008 PMID: 18954261 ). |
Essential region mapped to C3b binding site on CR1 (Rowe et al., 2000 PMID: 11086071 ) |
|
|
CR1 Knops blood group polymorphisms associated with severe malaria (Opi et al., 2018 PMID: 29690995) |
|
|
HEPARAN SULFATE (HS)** |
Glycosaminoglycan |
Heparin partially disrupts rosettes in some isolates (Udomsangpetch et al., 1989 PMID: 2654325; Carlson et al., 1992 PMID: 1599054; Rogerson et al., 1994 PMID: 7521140; Rowe et al., 1994 PMID: 8001661; Barragan et al., 1999 PMID: 9990341) |
Limited evidence that HS is present on mature RBCs (Vogt et al., 2004 PMID: 15209561) |
|
Heparin is a highly sulfated form of HS that is only found in mast cells |
Heparinase treatment reported to reduce rosetting in two culture-adapted parasite lines (Barragan et al., 1999 PMID: 9990341) |
Further work needed to determine whether HS is present on normal erythrocytes and acts as a rosetting receptor |
|
HS is a receptor for P. falciparum sporozoite invasion of hepatocytes (ב |
Heparin binds to rosetting iRBCs (Barragan et al., 2000a; Heddini et al., 2001) and to rosette-mediating PfEMP1 (Barragan et al., 2000a PMID: 10828049; Vogt et al., 2003 PMID: 1243368; Juillerat et al., 2010 PMID: 20045435 ; Juillerat et al., 2011 PMID: 21402930; Adams et al., 2014 PMID: 24343658 ) |
Therapeutic potential due to PfEMP1 binding and rosette disruption. Clinical trials of low anticoagulant heparin ongoing (Leitgeb et al., 2017 PMID: 29244851) |
|
HS is a receptor for infected erythrocyte cytoadherence to endothelial cells (Vogt et al., 2003 PMID: 1243368; Adams et al., 2014 PMID: 24343658 ) |
Soluble CS did not disrupt rosettes (Rogerson et al., 1994 PMID: 752114; Rowe et al., 1994 PMID: 8001661) |
|
CHONDROITIN SULFATE (CS) |
Glycosaminoglycan |
Chondroitinase treatment reduced rosetting in one parasite line only (Barragan et al., 1999 PMID: 9990341) |
No evidence that CS is present on mature RBC |
|
Receptor for infected erythrocyte placental sequestration in pregnancy malaria (Fried & Duffy, 1996 PMID: 8633247) |
|
Minimal evidence for a role in rosetting |
CD36 |
Widely distributed membrane protein and scavenger receptor (Silverstein & Febbraio, 2009 PMID: 19471024) |
Antibodies disrupt rosettes in single culture-adapted line only (Handunnetti et al., 1992) |
Minimal evidence for a widespread role in rosetting |
|
Deficiency is common in Africa but not associated with severe malaria (Fry et al., 2009 PMID: 19403559) |
PfEMP1 variants that mediate rosetting are group A types that do not bind CD36 (Robinson et al., 2003 PMID: 12603733) |
|
GLYCOPHORIN C (GYPC) |
Red cell membrane protein responsible for Gerbich blood group (Jaskiewicz et al., 2018 PMID: 29540278) |
Reduced rosetting with GYPC antibodies and GYPC knockdown RBCs (Niang et al., 2014 PMID: 25011110) (single culture-adapted parasite line tested) |
Further work needed to assess the relative importance of GYPC in P. falciparum rosetting isolates and potential as a therapeutic target |
|
Receptor for merozoite invasion of erythrocytes (Maier et al., 2003 PMID: 1646190) |
Gerbich negative erythrocytes formed rosettes normally with five P. falciparum lines (Rowe et al., 1997 PMID: 9230440). |
|
|
“Gerbich negative” blood group common in Melanesians (Patel et al., 2001 PMID: 11719395), but no evidence yet for association with protection against severe malaria. |
Possible role in P. vivax rosetting (Lee et al., 2014 PMID: 24652986) |
|
GLYCOPHORIN A (GYPA) |
Sialoglycoprotein which, along with Glycophorin B, constitutes the MNS blood group |
GYPA deficient erythrocytes showed reduced rosetting with RIFIN transfected parasites (Goel et al., 2015 PMID: 25751816) |
Further work needed to assess the relative importance of GYPA in P. falciparum rosetting isolates and potential as a therapeutic target |
|
Receptor for merozoite invasion of erythrocytes (Sim et al., 1994 PMID: 8009226) |
GYPA antibodies had no inhibitory effect on rosetting (Lee et al., 2014 PMID: 24652986) (Niang et al., 2014 PMID: 25011110) |
|
|
GYPA polymorphisms are associated with protection against severe malaria (Band et al., 2015 PMID: 2641675; Leffler et al., 2017). |
GYPA null erythrocytes formed rosettes with five culture-adapted P. falciparum lines (Rowe et al., 1997 PMID: 9230440 ) |
|
UNKNOWN RECEPTOR/S |
Possibly carbohydrate or protease-resistant protein |
Protease and heparinase treated erythrocytes capable of forming rosettes (Udomsangpetch et al., 1989 PMID: 2654325; Rowe et al., 1994 PMID: 8001661) |
Further work needed to identify novel rosetting receptors |
*Note: Parasite strains used are not consistent between studies with a wide range of culture-adapted and clinical isolates in use. Results are therefore not necessarily generalizable from single studies. |
**Note: Many studies included here use heparin instead of/in addition to heparan sulfate |
|
|
|
|
|
|
|
|
|
|
|
|
|
Adams et al., 2014 |
PMID: 24343658 |
|
|
Band et al., 2015 |
PMID: 2641675 |
|
|
Barragan et al., 1999 |
PMID: 9990341 |
|
|
Barragan et al., 2000a |
PMID: 10828049 |
|
|
Barragan et al., 2000b |
PMID: 10768996 |
|
|
Carlson & Wahlgren, 1992 |
PMID: 1402677 |
|
|
Carlson et al., 1992 |
PMID: 1599054 |
|
|
Cockburn et al., 2004 |
PMID: 14694201 |
|
|
Degarege et al., 2019 |
PMID: 30029997 |
|
|
Fried & Duffy, 1996 |
PMID: 8633247 |
|
|
Fry et al., 2008 |
PMID: 18003641 |
|
|
Fry et al., 2009 |
PMID: 19403559 |
|
|
Goel et al., 2015 |
PMID: 25751816 |
|
|
Handunnetti et al., 1992 |
PMID: 1382720 |
|
|
Heddini et al., 2001 |
PMID: 11500463 |
|
|
Jaskiewicz et al., 2018 |
PMID: 29540278 |
|
|
Juillerat et al., 2010 |
PMID: 20045435 |
|
|
Juillerat et al., 2011 |
PMID: 21402930 |
|
|
Lee et al., 2014 |
PMID: 24652986 |
|
|
Leffler et al., 2017 |
PMID: 28522690 |
|
|
Leitgeb et al., 2017 |
PMID: 29244851) |
|
|
Li et al., 2006 |
PMID: 17081086 |
|
|
Ndila et al., 2018 |
PMID: 30033078 |
|
|
Niang et al., 2014 |
PMID: 25011110 |
|
|
Niang et al., 2014 |
PMID: 25011110 |
|
|
Opi et al., 2018 |
PMID: 29690995 |
|
|
Panda et al., 2012 |
PMID: 23152904 |
|
|
Patel et al., 2001 |
PMID: 11719395 |
|
|
Reddy et al., 2017 |
PMID: 27977428 |
|
|
Robinson et al., 2003 |
PMID: 12603733 |
|
|
Rogerson et al., 1994 |
PMID: 752114 |
|
|
Rout et al., 2011 |
PMID: 22818742 |
|
|
Rowe et al., 1994 |
PMID: 8001661 |
|
|
Rowe et al., 1995 |
PMID: 7768616 |
|
|
Rowe et al., 1997 |
PMID: 9230440 |
|
|
Rowe et al., 2000 |
PMID: 11086071 |
|
|
Rowe et al., 2007 |
PMID: 17959777 |
|
|
Schmidt et al., 2015 |
PMID: 25816986 |
|
|
Silverstein & Febbraio, 2009 |
PMID: 19471024 |
|
|
Sim et al., 1994 |
PMID: 8009226 |
|
|
Sinha et al., 2009 |
PMID: 19480840 |
|
|
Tekeste & Petros 2010 |
PMID: 20939876 |
|
|
Thielen et al., 2018 |
PMID: 29397262 |
|
|
Udomsangpetch et al., 1989 |
PMID: 2654325 |
|
|
Udomsangpetch et al., 1993 |
PMID: 8447516 |
|
|
Vigan-Womas et al., 2012 |
PMID: 22807674 |
|
|
Vogt et al., 2003 |
PMID: 1243368 |
|
|
Vogt et al., 2004 |
PMID: 15209561 |
|
|
|
|
|
|