Immunization with a tetramer derivative of an anti‐inflammatory pentapeptide produced by Entamoeba histolytica protects gerbils (Meriones unguiculatus) against experimental amoebic abscess of the liver

Abstract

Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with several anti-inflammatory properties, including the inhibition of human monocyte locomotion (Monocyte Locomotion Inhibitory Factor (MLIF)). A construct displays the same effects as the native material. It remains to be seen if MLIF is used, or even produced in vivo by the tissue-invading parasite. If MLIF were to be relevant in invasive amoebiasis, immunizing against it could diminish this parasite advantage and prevent lesions. KLH-linked MLIF mixed with Freund's adjuvant was too aggressive an immunizing material to answer this question. However, immunization with a tetramer of MLIF (but not a scrambled version of MLIF) around a lysine core (MLIF-MAPS), that displays increased antigenicity, yet lacks excessive innate immunity activation, completely protects gerbils against amoebic abscess of the liver caused by the intraportal injection of virulent E. histolytica. Liver abscesses caused by Listeria monocytogenes were not prevented. Invasive E. histolytica may produce the parent protein of MLIF in vivo, and if appropriately cleaved, it may play a role in invasive amoebiasis. MLIF may join new vaccination strategies against amoebiasis.

Amebic monocyte locomotion inhibitory factor peptide ameliorates inflammation in CIA mouse model by downregulation of cell adhesion, inflammation/chemotaxis, and matrix metalloproteinases genes

“…The origin and striking multiplicity of the biological actions of MLIF can be understood by its apparent effect on NF-jB [5] and the MAPK signaling pathway (see Electronic supplementary material). Some studies support the clinical antiinflammatory effects of MLIF on inflammatory processes [2,4,17]. However, to our knowledge, this is the first study that has evaluated the effects of MLIF in a comprehensive manner using a wellestablished model of inflammatory disease such as CIA.…”

The Role of Lipopeptidophosphoglycan in the Immune Response toEntamoeba histolytica

“…MLIF also decreased interleukin- (IL-) 1beta and increased IL-10 production by PMA-stimulated human CD4 T lymphocytes [35]. Immunization with a tetramer of MLIF around a lysine core completely protected gerbils ( Meriones unguiculatus ) against amebic liver abscess [36]. …”

The monocyte locomotion inhibitory factor inhibits the expression of inflammation‐induced cytokines following experimental contusion in rat tibia

“…The pentapeptide also inhibits the respiratory burst and production of nitric oxide in human monocytes and neutrophils, decreases expression of adhesion molecules (VL‐4 in monocytes and VCAM‐1 in vascular endothelium) and inhibits delayed hypersensitivity in gerbils and guinea pigs . A pentapeptide composed of the same amino acids, but in a different sequence (MLIF scramble, Gln‐Cys‐Met‐Ser‐Asn), presents no anti‐inflammatory properties . Such an effect may be attributable to the chemical activity of the peptide.…”