Cathelicidin Contributes to the Restriction of Leishmania in Human Host Macrophages

In cutaneous Leishmaniasis the parasitic control in human host macrophages is still poorly understood. We found an increased expression of the human cathelicidin CAMP in skin lesions of Ethiopian patients with cutaneous leishmaniasis. Vitamin D driven, Cathelicidin-type antimicrobial peptides (CAMP) play an important role in the elimination of invading microorganisms. Recombinant cathelicidin was able to induce cell-death characteristics in Leishmania in a dose dependent manner. Using human primary macrophages, we demonstrated pro-inflammatory macrophages (hMDM1) to express a higher level of human cathelicidin, both on gene and protein level, compared to anti-inflammatory macrophages (hMDM2). Activating the CAMP pathway using Vitamin D in hMDM1 resulted in a cathelicidin-mediated-Leishmania restriction. Finally, a reduction of cathelicidin in hMDM1, using a RNA interference (RNAi) approach, increased Leishmania parasite survival. In all, these data show the human cathelicidin to contribute to the innate immune response against Leishmaniasis in a human primary cell model.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
Leishmania
human macrophages
vitamin D
cathelicidin (LL-37)
human
primary immune cells
antimicrobial activity
vitamin-d-receptor
nitric-oxide
cutting edge
antimicrobial peptides
immune-response
camp gene
ll-37
infection
skin
induction
Immunology

Bank, E. (author)
Walber, B. (author)
Wenzel, Ulf Alexander,1975Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xwenal (author)
Agerberth, B.Karolinska Institutet (author)
Chanyalew, M. (author)
Abebe, M. (author)
Konig, R. (author)
Ritter, U. (author)
Reiling, N. (author)
van Zandbergen, G. (author)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för mikrobiologi och immunologi (creator_code:org_t)

By the author/editor: Crauwels, P.; Bank, E.; Walber, B.; Wenzel, Ulf Alex ...; Agerberth, B.; Chanyalew, M.; show more...; Abebe, M.; Konig, R.; Ritter, U.; Reiling, N.; van Zandbergen, ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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