Abstract
Blockade of IL-10 signalling clears chronic viral and bacterial infections. Immunization together with blockade of IL-10 signalling or relatively low level of IL-10 further enhances viral and bacterial clearance. IL-10 functions through binding to interleukin 10 receptor (IL-10R). Here we showed that peptides P1 and P2 with the hydrophobic and hydrophilic pattern of the IL10R-binding helix in IL-10 could bind with either IL-10R1 or IL-10, and inhibit inflammatory signals with long duration and negligible cytotoxicity in vitro. Furthermore, P2 can enhance antigen specific CD8+ T cell responses in mice induced by the vaccine based on a long peptide of protein E7 in a human papillomavirus type 16.
Highlights
Interleukin 10 (IL-10) is an anti-inflammatory cytokine with multiple biological functions
There are significantly more electron negative oxygen atoms than acidic hydrogens in IL10-R binding residues, we speculated that peptide sequenced with more of acidic hydrogens would favour its interference with IL-10/IL-10 receptor (IL-10R) interaction
Because P2 can enhance IL-12 secretion by LPS stimulated human peripheral blood mononuclear cells (PBMCs) in vitro (Fig 5), we investigated whether P2 is bioactive ex vivo by using a mouse vaccination model based on early protein 7 (E7) long peptide/Incomplete Freund’s adjuvant (IFA) of human papillomavirus type 16 [63]
Summary
Interleukin 10 (IL-10) is an anti-inflammatory cytokine with multiple biological functions. Its expression level is elevated during persistent viral infections such as human immunodeficiency virus (HIV), hepatitis B and hepatitis C (HBV, HCV) in humans [1,2,3]. IL-10 blockade has been shown to enhance T cell responses which in turn control persistent infection of lymphocytic choriomeningitis virus or cytomegalovirus [3,4,5] in mice. Immunization in conjunction with blockade of IL-10 signalling increases vaccine-induced T cell responses and clears bacteria, parasite and chronic viral infection more efficiently than that with IL-10/IL-10R at normal or over-expression levels[2, 6,7,8,9]. Blocking IL-10 signalling at the time of immunization is able to control tumour growth in mouse model [10, 11]. IL-10 knockout mice develops chronic inflammation in intestine only in late life stage, suggesting that temporal blocking
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