Abstract
Background:
Scavenger Receptors (SRs) from the host's innate immune system are known to bind multiple ligands to promote the removal of non-self or altered-self targets. CD5 and CD6 are two highly homologous class I SRs mainly expressed on all T cells and the B1a cell subset, and involved in the fine tuning of activation and differentiation signals delivered by the antigen-specific receptors (TCR and BCR, respectively), to which they physically associate. Additionally, CD5 and CD6 have been shown to interact with and sense the presence of conserved pathogen-associated structures from bacteria, fungi and/or viruses.
Methodology/principal findings:
We report herein the interaction of CD5 and CD6 lymphocyte surface receptors with Echinococcus granulosus sensu lato (s.l.). Binding studies show that both soluble and membrane-bound forms of CD5 and CD6 bind to intact viable protoscoleces from E. granulosus s.l. through recognition of metaperiodate-resistant tegumental components. Proteomic analyses allowed identification of thioredoxin peroxidase for CD5, and peptidyl-prolyl cis-trans isomerase (cyclophilin) and endophilin B1 (antigen P-29) for CD6, as their potential interactors. Further in vitro assays demonstrate that membrane-bound or soluble CD5 and CD6 forms differentially modulate the pro- and anti-inflammatory cytokine release induced following peritoneal cells exposure to E. granulosus s.l. tegumental components. Importantly, prophylactic infusion of soluble CD5 or CD6 significantly ameliorated the infection outcome in the mouse model of secondary cystic echinococcosis.
Conclusions/significance:
Taken together, the results expand the pathogen binding properties of CD5 and CD6 and provide novel evidence for their therapeutic potential in human cystic echinococcosis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, CD / genetics
-
Antigens, CD / metabolism*
-
Antigens, Differentiation, T-Lymphocyte / genetics
-
Antigens, Differentiation, T-Lymphocyte / metabolism*
-
CD5 Antigens / genetics
-
CD5 Antigens / metabolism*
-
Echinococcosis / genetics
-
Echinococcosis / metabolism*
-
Echinococcosis / parasitology
-
Echinococcus granulosus / genetics
-
Echinococcus granulosus / metabolism*
-
Female
-
Helminth Proteins / genetics
-
Helminth Proteins / metabolism*
-
Humans
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Protein Binding
-
Proteomics
-
Receptors, Scavenger / genetics
-
Receptors, Scavenger / metabolism*
-
T-Lymphocytes / metabolism
-
T-Lymphocytes / parasitology
Substances
-
Antigens, CD
-
Antigens, Differentiation, T-Lymphocyte
-
CD5 Antigens
-
CD6 antigen
-
Helminth Proteins
-
Receptors, Scavenger
Grants and funding
The work by FL’s group is supported by grants from Spanish Ministerio de Economía y Competitividad (MINECO, Plan Nacional I+D+i, SAF2016-80535-R and PCIN-2015-070 under the project SRecognite Infect-ERA/0003/2015 - co-financed by European Development Regional Fund “A way to achieve Europe” ERDF) and Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR; 2017/SGR/1582) from Generalitat de Catalunya. MV-DA is recipient of a pre-doctoral fellowship from Spanish MINECO (BES-2014-069237). The work by GM-E’s group is supported by a grant from Uruguayan Agencia Nacional de Investigación e Innovación (ANII, FCE-1-2017-1-135537), and general financial funding from CSIC (Universidad de la República, Uruguay) and PEDECIBA-Química (Uruguay). SM is recipient of a pre-doctoral fellowship from Comisión Académica de Posgrado (CAP, Universidad de la República, Uruguay). GM-E received a short-stage post-doctoral fellowship from Spanish Fundación Carolina. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.