Cathelicidin Contributes to the Restriction of Leishmania in Human Host Macrophages

Crauwels, Peter; Bank, Elena; Walber, Bianca; Wenzel, Ulf Alexander; Agerberth, Birgitta; Chanyalew, Menberework; Abebe, Markos; König, Renate; Ritter, Uwe; Reiling, Norbert; Zandbergen, Ger van

doi:10.3389/fimmu.2019.02697

Cited by 22 publications

(16 citation statements)

References 61 publications

(61 reference statements)

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“…LL37, the bioactive cleavage product of human cationic antimicrobial protein (hCAP18) that is encoded by CAMP, caused apoptosis of L. aethiopica and L. major promastigotes in vitro . Treatment of human macrophages (derived from rhGM-CSF-treated monocytes) with 1α,25-dihydroxyvitamin D3 enhanced CAMP mRNA expression and the production of hCAP18, which was paralleled by reduced survival of intracellular Leishmania [175] .…”

Section: Macrophages As Antileishmanial Effector Cells In Leishmaniasmentioning

confidence: 97%

Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism

Bogdan

2020

Cytokine: X

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Highlights Macrophages serve as replicative niche, antimicrobial effectors or immunoregulators. Functional diversity results from cytokines, micromilieu factors and metabolites. Micro milieu factors include hypoxia, tonicity and amino acid availability. Leishmania reprogram the transcription, translation and metabolism of macrophages.

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Section: Macrophages As Antileishmanial Effector Cells In Leishmaniasmentioning

confidence: 97%

Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism

Bogdan

2020

Cytokine: X

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“…To better understand how CRAMP can protect when orally administered to neonatal mice, we next investigated the antimicrobial effectivity of CRAMP on C. parvum. CRAMP displays antimicrobial activity against different bacteria, fungi, and also parasites such as Leishmania [ 34 ]. Three hours after exposure to CRAMP, viable sporozoites were stained with CFDA-SE and analyzed by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

“…Despite their important role described in fighting pathogens, they have been poorly investigated in parasitic infections. In vitro, LL37 was shown to contribute to the restriction of Leishmania development in THP1cells [ 35 ] and in primary human macrophages [ 34 ]. Moreover, Plasmodium yoelii and Trypanosoma viability and cellular multiplication are reduced when exposed to LL37 [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Cryptosporidium parvum Subverts Antimicrobial Activity of CRAMP by Reducing Its Expression in Neonatal Mice

et al. 2020

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Cryptosporidium parvum causes diarrhea in infants under 5 years, in immunosuppressed individuals or in young ruminants. This parasite infects the apical side of ileal epithelial cells where it develops itself and induces inflammation. Antimicrobial peptides (AMPs) are part of the innate immune response, playing a major role in the control of the acute phase of C. parvum infection in neonates. Intestinal AMP production in neonates is characterized by high expressions of Cathelicidin Related Antimicrobial Peptide (CRAMP), the unique cathelicidin in mice known to fight bacterial infections. In this study, we investigated the role of CRAMP during cryptosporidiosis in neonates. We demonstrated that sporozoites are sensitive to CRAMP antimicrobial activity. However, during C. parvum infection the intestinal expression of CRAMP was significantly and selectively reduced, while other AMPs were upregulated. Moreover, despite high CRAMP expression in the intestine of neonates at homeostasis, the depletion of CRAMP did not worsen C. parvum infection. This result might be explained by the rapid downregulation of CRAMP induced by infection. However, the exogenous administration of CRAMP dampened the parasite burden in neonates. Taken together these results suggest that C. parvum impairs the production of CRAMP to subvert the host response, and highlight exogenous cathelicidin supplements as a potential treatment strategy.

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“…Recently, CAMP has been described to act as anti-oncogenic agent in breast cancer [101]. Regarding cutaneous leishmaniasis (CL), a study in Ethiopian patients proved the existence of high expression of CAMP in skin lesions [102].…”

Section: Cathelicidin 231 Cathelicidin and Leishmaniamentioning

confidence: 99%

Activity of Anti-Microbial Peptides (AMPs) against Leishmania and Other Parasites: An Overview

et al. 2021

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Anti-microbial peptides (AMPs), small biologically active molecules, produced by different organisms through their innate immune system, have become a considerable subject of interest in the request of novel therapeutics. Most of these peptides are cationic-amphipathic, exhibiting two main mechanisms of action, direct lysis and by modulating the immunity. The most commonly reported activity of AMPs is their anti-bacterial effects, although other effects, such as anti-fungal, anti-viral, and anti-parasitic, as well as anti-tumor mechanisms of action have also been described. Their anti-parasitic effect against leishmaniasis has been studied. Leishmaniasis is a neglected tropical disease. Currently among parasitic diseases, it is the second most threating illness after malaria. Clinical treatments, mainly antimonial derivatives, are related to drug resistance and some undesirable effects. Therefore, the development of new therapeutic agents has become a priority, and AMPs constitute a promising alternative. In this work, we describe the principal families of AMPs (melittin, cecropin, cathelicidin, defensin, magainin, temporin, dermaseptin, eumenitin, and histatin) exhibiting a potential anti-leishmanial activity, as well as their effectiveness against other microorganisms.

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Cathelicidin Contributes to the Restriction of Leishmania in Human Host Macrophages

Cited by 22 publications

References 61 publications

Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism

Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism

Cryptosporidium parvum Subverts Antimicrobial Activity of CRAMP by Reducing Its Expression in Neonatal Mice

Activity of Anti-Microbial Peptides (AMPs) against Leishmania and Other Parasites: An Overview

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