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Hanna Jarva

Publications and source records attributed to Hanna Jarva.

6 recordsLinked to original sources
PubMed2004

The group B streptococcal beta and pneumococcal Hic proteins are structurally related immune evasion molecules that bind the complement inhibitor factor H in an analogous fashion.

Complement evasion by different mechanisms is important for microbial virulence and survival in the host. One strategy used by pathogenic bacteria is to bind the soluble complement inhibitor factor H (fH) to their surfaces. In group B streptococci and pneumococci, fH binding has been shown to be mediated by the surface proteins beta and Hic, respectively. We showed previously that Hic binds to the middle region of fH and protects the pneumococcus from opsonophagocytosis. As the beta protein and Hic are structurally closely related, we wanted to compare the fH binding characteristics of these two proteins. By using direct binding assays with radiolabeled proteins and surface plasmon resonance analysis we show that both beta and Hic bind to the short consensus repeats 8-11 and 12-14 in the middle region of fH. Peptide mapping analysis suggested that the fH-binding sites on beta and Hic were composed of discontinuous and partially homologous sequences. Thus, the bacterial virulence proteins use multiple binding sites on fH to secure high avidity. Also, the functionally active sites on fH are thereby left free to inhibit C3b deposition and opsonophagocytosis. These results reveal the evolutionary conservation of an analogous immune evasion strategy in different types of pathogenic streptococci. Importantly, the respective virulence factors could be exploited in the development of protein-based vaccines against these pathogens.

Amino Acid Sequence↗
PubMed2003

Association between complement factor H and proteoglycans in early human coronary atherosclerotic lesions: implications for local regulation of complement activation.

OBJECTIVE: Complement activation has been suggested to play a role in atherogenesis. To study the regulation of complement activation in human coronary atherosclerotic lesions, we examined the spatial relationships between the major complement inhibitor, factor H, and the complement activation products C3d and C5b-9. METHODS AND RESULTS: In early lesions (American Heart Association types II and III), factor H was immunohistochemically found in the superficial proteoglycan-rich layer in association with numerous macrophages and C3d, whereas C5b-9 was found deeper in the intima, where factor H was virtually absent. In vitro experiments involving surface plasmon resonance and affinity chromatography analyses demonstrated that isolated human arterial proteoglycans bind factor H, and functional complement assays showed that glycosaminoglycans inhibit the complement activation induced by modified low density lipoprotein or by a foreign surface. CONCLUSIONS: The present observations raise the possibility that proteoglycans, because of their ability to bind the major complement inhibitor factor H, may inhibit complement activation in the superficial layer of the arterial intima. In contrast, deeper in the intima, where factor H and proteoglycans are absent, complement may be activated and proceed to C5b-9. Thus, the superficial and the deep layers of the human coronary artery appear to differ in their ability to regulate complement activation.

Adult↗
PubMed2003

Complement resistance mechanisms of streptococci.

Group A streptococcus (GAS, Streptococcus pyogenes), group B streptococcus (GBS, Streptococcus agalactiae) and pneumococcus (Streptococcus pneumoniae) are all human pathogens that cause significant morbidity and mortality worldwide. These related species cause different spectra of infections spanning from trivial upper respiratory tract or skin infections to septic and severe diseases. In order to cause deep infections and survive in the human body the bacteria must evade the immune system. Complement is an important part of innate immunity both as an opsonizing and membrane destructing cascade and as an effector system of antibodies. In this review, we describe the complement resistance mechanisms of the three clinically most important streptococcal species, groups A and B streptococci and pneumococcus. The complement evasion mechanisms of these three species are analogous, yet different from one another. Several strains of all three species express molecules (M-proteins, Bac or beta, PspC) that acquire host fluid-phase complement regulators factor H or C4b binding protein to their surfaces. Groups A and B streptococci also secrete proteins and/or enzymes that inhibit the activation of the complement system or chemotaxis caused by the complement activation products. Even though a lot is known about the immune evasion by streptococci, the high morbidity and mortality associated with infections caused by streptococci and the need for efficient vaccines warrant further studies on the streptococcal molecules mediating complement resistance.

Animals↗
PubMed2002

Binding of C-reactive protein to modified low-density-lipoprotein particles: identification of cholesterol as a novel ligand for C-reactive protein.

C-reactive protein (CRP), an acute-phase reactant, is present in atherosclerotic human arterial intima in association with lipids. In the present work we studied interactions between CRP and LDL on microtitre wells, where either CRP or LDL was immobilized. LDL was modified by vortex-mixing, oxidation, or by lipolysis with phospholipase A(2) or with sphingomyelinase or a combination of trypsin and cholesterol esterase. We found that CRP bound only to LDL modified by trypsin/cholesterol esterase or by sphingomyelinase and that this binding was Ca(2+)-dependent. In these two forms of modified LDL, non-esterified cholesterol was susceptible to cholesterol oxidase, indicating exposure of non-esterified cholesterol on particle surfaces and suggesting a role for non-esterified cholesterol in mediating CRP binding. Consistent with this hypothesis were the following findings: (i) increasing the amount of non-esterified cholesterol in LDL with cyclodextrin increased, and decreasing its amount decreased, the binding of CRP to LDL; (ii) modification of non-esterified cholesterol in LDL by cholesterol oxidase decreased the binding of CRP to LDL; and (iii) CRP bound to purified non-esterified cholesterol. The binding was Ca(2+)-dependent and could be competed out with phosphocholine. Taken together, these findings suggest that CRP can bind to modified lipoproteins, notably to the non-esterified cholesterol on their surface. These interactions may be related to the suggested role of CRP in the local inflammation present in atherosclerotic plaques.

Arteriosclerosis↗
PubMed2002

Streptococcus pneumoniae evades complement attack and opsonophagocytosis by expressing the pspC locus-encoded Hic protein that binds to short consensus repeats 8-11 of factor H.

Streptococcus pneumoniae is an important cause of upper and lower respiratory tract infections, meningitis, peritonitis, bacterial arthritis, and sepsis. Here we have studied a novel immune evasion mechanism of serotype 3 pneumococci, which are particularly resistant to phagocytosis. On their surfaces the bacteria express the factor H-binding inhibitor of complement (Hic), a protein of the pneumococcal surface protein C family. Using radioligand binding, microtiter plate assays, surface plasmon resonance analysis, and recombinant constructs of factor H, we located the binding site of Hic to short consensus repeats (SCRs) 8-11 in the middle part of factor H. This represents a novel microbial interaction region on factor H. The only other ligand known so far for SCRs 8-11 of factor H is C-reactive protein (CRP), an acute phase protein that binds to the pneumococcal C-polysaccharide. The binding sites of Hic and CRP within the SCR8-11 region were different, however, because CRP did not inhibit the binding of Hic and required calcium for binding. Binding of factor H to Hic-expressing pneumococci promoted factor I-mediated cleavage of C3b and restricted phagocytosis of pneumococci. Thus, virulent pneumococci avoid complement attack and opsonophagocytosis by recruiting functionally active factor H with the Hic surface protein. Hic binds to a previously unrecognized microbial interaction site in the middle part of factor H.

Bacterial Proteins↗