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Posted by marga_goris on 04 Apr 2011 at 10:25 GMT
Leptospirosis is a world-wide zoonosis with a considerable impact on veterinary and human public health. Little is know about its pathogenesis. The innate immune system forms the first barrier in the host defense against infection. Several signaling (cytokines) and receptor molecules such as the Toll-like receptor (TLR) are involved in triggering the innate immune system. TLRs respond to certain effector molecules; TLR2 usually to lipoproteins, TLR4 to LPS and TLR5 to flagella. Previous studies demonstrated a role of human TLR2, and not TLR4, for recognition of leptospiral LPS. Murine models demonstrated stimulation of both TLR2 and TLR4 by heat-killed and viable Leptospira. We hypothesized that models using fragments of infectious agents and selections of blood cells such as monocytic cells or a murine model may not provide a reflection of the mechanisms that occur in the physiological situation in humans. Therefore, we investigated innate immune responses to viable virulent and non-virulent leptospires in human whole blood. Here we demonstrate (i) the importance of using low passage virulent leptospiral isolates, (ii) high cytokine releases by virulent living Leptospira in human whole blood, (iii) differences in cytokine releases in different models using monocytic cells, peripheral blood mononuclear cells or whole blood and, (iv) the involvement of TLR2, TLR4 and TLR5 in the response to Leptospira by human blood. Our observations are highly relevant for further studies on innate immune responses.