The dermatophyte arthroderma benhamiae uses two strategies to control complement in skin

Schindler, Susann GND

Dermatophytes cause superficial infections of the upper layers of the skin. In skin they get in contact with keratinocytes. This work shows that keratinocytes secrete a functional complement system. Keratinocyte derived C3b opsonises conidia of the dermatophyte A. benhamiae, which leads to an increase of phagocytosis by human monocytes. Former studies showed that dermatophytes exhibit resistence against complement. To avoid complement activation the fungus aquires keratinocyte derived complement regulatory proteins, such as Factor H and CFHR1 on its surface. Fungal bound Factor H mediate cleavage of the central complement component C3b. The degradation leads to an inactivation of C3b and thus to the decrease of opsonophagocytosis of the conidia. Furthermore C3b cleavage results in the inhibition of the following complement cascade and avoids the formation of the anaphylatoxins C3a, C4a and C5a, as well as the formation of the lytic terminal complement complex. A. benhamiae secretes after in vitro stimulation with keratin a multiplicity of proteases in the culture supernatant. This study shows that A. benhamiae secreted proteases cleave the complement proteins C3, C3b, C4, C4b, C5, C6 and of the anaphylatoxins C3a and C5a and leads to the inactivation of the respective complement effector function. The proteolytic activity of A. benhamiae inactivates C3b and thus opsonophagocytosis of fungal conidia. The cleavage of C3, C4, C5 and C6 blocks the formation of the terminal complement complex on surfaces and consequently the lysis of complement sensitive cells. Moreover A. benhamiae derived proteases inhibit the antifungal and anaphylactic properties of C3a and C5a. Thereby the serine protease Subtilisin 3 was identified as major complement degrading protease in the supernatant of an A. benhamiae culture. Complement inactivation by acquiring human complement regulators or endogenous proteolytic activity of A. benhamiae are timely separated mechanisms.

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Schindler, Susann: The dermatophyte arthroderma benhamiae uses two strategies to control complement in skin. 2012.

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