Recombinant CD5 and CD6 Ectodomains Induce Antiparasitic and Immunomodulatory Effects in Secondary Cystic Echinococcosis

Author:

García‐Luna Joaquín1234,Rivero‐Osorio Florencia123,González‐Porcile María Clara1235,Arbildi Paula123ORCID,Miles Sebastián1234,Magnone Javier1234,Velasco‐De‐Andrés María6,Dematteis Sylvia123,Lozano Francisco678,Mourglia‐Ettlin Gustavo123ORCID

Affiliation:

1. Área Inmunología, Departamento de Biociencias (DEPBIO), Facultad de Química Universidad de la República Montevideo Uruguay

2. Unidad Asociada de Inmunología, Facultad de Ciencias Instituto de Química Biológica (IQB), Universidad de la República Montevideo Uruguay

3. Laboratorio de Inmunología Instituto de Higiene ‘Prof. Arnoldo Berta’, Universidad de la República Montevideo Uruguay

4. Graduate Program in Chemistry, Facultad de Química Universidad de la Republica Montevideo Uruguay

5. Graduate Program in Biotechnology, Facultad de Ciencias Universidad de la Republica Montevideo Uruguay

6. Group of Immunoreceptors of the Innate and Adaptive System Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona Spain

7. Departament de Biomedicina, Facltuat de Medicina Universitat de Barcelona Barcelona Spain

8. Servei d'Immunologia Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona Barcelona Spain

Abstract

ABSTRACTScavenger receptors participate in a wide range of biological functions after binding to multiple non‐self or altered self‐ligands. Among them, CD5 and CD6 are lymphocyte scavenger receptors known to interact with different microbial‐associated molecular patterns, and the administration of the recombinant soluble ectodomains of human CD5 (rshCD5) and/or CD6 (rshCD6) has shown therapeutic/prophylactic potential in experimental models of fungal, bacterial and echinococcal infections. The latter is a zoonosis caused by the larval stage of the cestode parasite Echinococcus granulosus sensu lato, which in humans can induce secondary cystic echinococcosis (CE) after the spillage of protoscoleces contained within fertile cysts, either spontaneously or during surgical removal of primary hydatid cysts. Herein, we have analysed the mechanisms behind the significant protection observed in the mouse model of secondary CE following prophylactic administration of rshCD5 or rshCD6. Our results show that both molecules exhibit intrinsic antiparasitic activities in vitro, as well as immunomodulatory functions during early secondary CE, mainly through Th1/Th17 cytokine bias and promotion of peritoneal polyreactive antibodies. These data support the relevance of the parasite components bound by rshCD5 and rshCD6, as well as the potential of their prophylactic administration as a useful strategy to reduce secondary CE in patients.

Funder

Programa de Desarrollo de las Ciencias Básicas

Universidad de la República Uruguay

Agencia Nacional de Investigación e Innovación

Publisher

Wiley

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