Investigation of lectin complement proteins in urinary schistosomiasis and visceral leishmaniasis

Abstract

Complement lectins are pathogen recognition receptors (PRRs) that bind to pathogen associated molecular patterns (PAMPs) of various microbes. The circulating serum levels and functional genetic variants of four such innate immune recognition elements, namely the human mannose-binding lectin (MBL), ficolin-2 (FCN2), collectin 11 (CL-K1), mannose-binding associated serine protease-2 (MASP2) were studied in intracellular (visceral leishmaniasis) and extracellular (urinary schistosomiasis) parasitic diseases. In extracellular Schistosoma haematobium infection, MBL, MASP2, and collectin-11 (CL- K1) and their functional variants were associated with relative protection. In intra-cellular Leishmania donovani infection, MBL, ficolin-2 and their functional variants were observed to be a susceptible host factor. IL-6 was observed to regulate the lectin expression during distinct parasitic infections. In conclusion, this dissertation provides probable evidence on the differential role of lectins in intra and extracellular infections.

Komplement-Lektine sind sogenannte “pathogen recognition receptors” (PRRs), welche Pathogen-assoziierte molekulare Muster (“pathogen associated molecular patterns”, PAMPs) diverser Krankheitserreger erkennen. Ich untersuchte zirkulierenden Serumlevel und funktionelle genetische Varianten von vier solcher PRRs in einer intrazellulären (viszerale Leishmaniose) und einer extrazellulären (urogenitale Schistosomiase) Krankheit: Mannose-bindendes Lektin (MBL), Ficolin 2 (FCN2), Collektin 11 (CL-K1), und MBL assoziierte Serinprotease 2 (MASP2). In der extrazellulären Schistosoma haematobium Infektion waren MBL, MASP2, und Collektin 11, sowie deren funktionelle Varianten mit einem relativen Schutz gegen die Krankheit assoziiert. In der intrazellulären Leishmania donovani Infektion waren MBL, Ficolin 2, und deren funktionelle Varianten Suszeptibilitätsfaktoren. Während distinkter parasitischer Infektionen regulierte IL-6 die Lektinexpression. Zusammenfassend erbringt diese Dissertation diverse Beweise für die differentielle Rolle von Lektinen in intra- und extrazellulären parasitischen Infektionen.