Lp95, a novel leptospiral protein that binds extracellular matrix components and activates e-selectin on endothelial cells

Atzingen, Marina V.; Gómez, Ricardo Martín; Schattner, Mirta; Pretre, Gabriela; Gonçales, Amane Paldês; Morais, Zenáide Maria de; Vasconcellos, Sílvio Arruda; Nascimento, Ana L. T. O.

doi:10.1016/j.jinf.2009.07.010

Cited by 49 publications

(45 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[8][9][10][11][12][13][14][15][16][17][18] Several laminin-binding proteins were identified, which indicated that leptospires have a redundant repertoire of adhesion molecules that are probably part of their invasion strategies. Lsa23, Lsa26, and Lsa36 bind laminin in a dose-dependent, specific, and saturable manner, fulfilling the properties of receptor-ligand interaction.…”

Section: Discussionmentioning

confidence: 99%

“…Some of these proteins were identified as novel leptospiral adhesins that might be involved in the first steps of host-Leptospira interaction. [8][9][10][11][12][13][14][15][16][17][18] After attachment, leptospires have to overcome tissue barriers and reach target organs. Proteolytic activity by plasmin (PLA) generation at the surface of Leptospira spp.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Three Novel Adhesins of Leptospira interrogans

Siqueira¹,

Atzingen²,

Alves³

et al. 2013

The American Society of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

Abstract. We report cloning, expression, purification, and characterization of three predicted leptospiral membrane proteins (LIC11360, LIC11009, and LIC11975). In silico analysis and proteinase K accessibility data suggest that these proteins might be surface exposed. We show that proteins encoded by LIC11360, LIC11009 and LIC11975 genes interact with laminin in a dose-dependent and saturable manner. The proteins are referred to as leptospiral surface adhesions 23, 26, and 36 (Lsa23, Lsa26, and Lsa36), respectively. These proteins also bind plasminogen and generate active plasmin. Attachment of Lsa23 and Lsa36 to fibronectin occurs through the involvement of the 30-kDa and 70-kDa heparin-binding domains of the ligand. Dose-dependent, specific-binding of Lsa23 to the complement regulator C4BP and to a lesser extent, to factor H, suggests that this protein may interfere with the complement cascade pathways. Leptospira spp. may use these interactions as possible mechanisms during the establishment of infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of Three Novel Adhesins of Leptospira interrogans

Siqueira¹,

Atzingen²,

Alves³

et al. 2013

The American Society of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

show abstract

“…A tight regulation of PMN migration is mandatory to permit pathogen elimination in the inflamed tissues. While few studies have indicated that endothelial cells can be activated in leptospirosis [16–18], little is known about the capacity of PMN to be activated and mobilized from the circulation to adhere to vessels and to infiltrate target organs.…”

Section: Introductionmentioning

confidence: 99%

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

et al. 2016

View full text Add to dashboard Cite

It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients.

show abstract

“…Two of them were described as novel adhesins, Lsa21 and Lp95 C-terminus region [18, 19], and the other two, rLIC10494 and rLIC12730, were shown to have a modest effect in immunoprotection studies [20]. The leptospiral genes, DnaK, LIC10368, LIC10494, LIC12730, and LIC12690, were genetically cloned in fusion with DnaK.…”

Section: Discussionmentioning

confidence: 99%

“…Among them were the adhesins Lsa21 [18], the C-terminus region of Lp95 [19], and two proteins rLIC12730 and rLIC10494. The two preceding proteins had their immunogenic and immunoprotective activities evaluated in hamsters and have shown only modest performance [20].…”

Section: Introductionmentioning

confidence: 99%

Induction of Boosted Immune Response in Mice by Leptospiral Surface Proteins Expressed in Fusion with DnaK

Atzingen

Rodríguez

Siqueira

et al. 2014

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Leptospirosis is an important global disease of human and veterinary concern. Caused by pathogenic Leptospira, the illness was recently classified as an emerging infectious disease. Currently available veterinarian vaccines do not induce long-term protection against infection and do not provide cross-protective immunity. Several studies have suggested the use of DnaK as an antigen in vaccine formulation, due to an exceptional degree of immunogenicity. We focused on four surface proteins: rLIC10368 (Lsa21), rLIC10494, rLIC12690 (Lp95), and rLIC12730, previously shown to be involved in host-pathogen interactions. Our goal was to evaluate the immunogenicity of the proteins genetically fused with DnaK in animal model. The chosen genes were amplified by PCR methodology and cloned into pAE, an E. coli vector. The recombinant proteins were expressed alone or in fusion with DnaK at the N-terminus. Our results demonstrate that leptospiral proteins fused with DnaK have elicited an enhanced immune response in mice when compared to the effect promoted by the individual proteins. The boosted immune effect was demonstrated by the production of total IgG, lymphocyte proliferation, and significant amounts of IL-10 in supernatant of splenocyte cell cultures. We believe that this approach could be employed in vaccines to enhance presentation of antigens of Leptospira to professional immune cells.

show abstract

Lp95, a novel leptospiral protein that binds extracellular matrix components and activates e-selectin on endothelial cells

Cited by 49 publications

References 55 publications

Characterization of Three Novel Adhesins of Leptospira interrogans

Characterization of Three Novel Adhesins of Leptospira interrogans

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

Induction of Boosted Immune Response in Mice by Leptospiral Surface Proteins Expressed in Fusion with DnaK

Contact Info

Product

Resources

About