Interaction of human complement factor H variants Tyr402 and His402 with leptospira spp

ABSTRACT

Leptospirosis isazoonosis caused by pathogenic bacteria from the genus Leptospira.Thediseaserepresents a seriouspublic health problem inunderdeveloped tropical countries.Leptospire sinfecthosts throughsmallabrasions in the skin or mucousmembranesand they rapidly disseminateto target organs.Thecapacityof some pathogenic leptospira lstrains toacquire thenegative complementregulators factorH(FH)andC4bbindingpro teincorrelateswith their abilityto survivein humans e rum.Inthis study weasses sed the functional consequences oft heagemaculardegeneration-associatedpolymorphismFHHis402orFHTyr402onFH Leptospira interactions.Inbinding assaysusing sub-satura tingamounts ofFH, theFHTyr402 variant interacted with all the strainstested more stronglythanthe FHHis402variant.Athigher concentrations, differences tendedto disappear. We then compared co factor activities displayed by FH. His402and FH Tyr402 bound tothe surface ofL.interrogans. Bothvariantsex ibit similar activity as cofactors for FactorI mediated cleavage of C3b,thusindicating that they do not differin their capacity toregulate the complement cascade.