Regulation of complement activation at the C3-level by serum resistant leptospires.
Leptospires are spirochetes that are transmitted to humans through contacts with wild or domestic animals or via an exposure to contaminated soil or water. In this study we have compared the serum-sensitivity of five pathogenic strains of leptospires (L. interrogans) to an environmental isolate (strain Patoc). Different levels of sensitivities to human serum were seen. Interestingly, the most sensitive strain was the non-pathogenic Patoc strain. The fully and intermediately resistant strains have been isolated from human patients. Testing was performed in the absence of specific antibodies, and killing was found to be dependent on the complement system. The serum sensitive Patoc strain was killed in human serum within minutes, whereas the most resistant strains tolerated serum up to 4h. We also tested the deposition of the complement components C3, C5, C6, C8 and C5b-9 to the surfaces of the sensitive and resistant strains of Leptospira by immunofluorescence microscopy and ELISA. C3 was deposited on both the sensitive and resistant strains, but the terminal complement components were detected only on the surface of the complement-sensitive strain. The complement resistant and intermediate strains were found to bind more factor H from human serum than the complement sensitive strain. Thus, binding of this major alternative complement pathway inhibitor is related to serum resistance in Leptospira spirochetes.
Meri
Taru
T
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, P.O. Box 21, 00014 Helsinki, Finland. taru.meri@helsinki.fi
Murgia
Rossella
R
Stefanel
Paola
P
Meri
Seppo
S
Cinco
Marina
M
D000818:Animals; D001770:Blood Bactericidal Activity; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism; D051056:Complement Inactivating Agents / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D007919:Leptospira / Q000145:classification / Q000378:metabolism / Q000472:pathogenicity*; D007921:Leptospira interrogans / Q000145:classification / Q000378:metabolism / Q000472:pathogenicity; D041383:Leptospira interrogans serovar icterohaemorrhagiae / Q000378:metabolism / Q000472:pathogenicity; D007922:Leptospirosis / Q000382:microbiology*; D051379:Mice; D014871:Water Microbiology
D003176:Complement C3; D051056:Complement Inactivating Agents; D015938:Complement Membrane Attack Complex; D017242:Complement Factor H; D003165:Complement System Proteins