CD6 deficiency impairs early immune response to bacterial sepsis
Cristina Català,
María Velasco-de Andrés,
Alejandra Leyton-Pereira,
Sergi Casadó-Llombart,
Manuel Sáez Moya,
Rebeca Gutiérrez-Cózar,
Joaquín García-Luna,
Marta Consuegra-Fernández,
Marcos Isamat,
Fernando Aranda,
Mario Martínez-Florensa,
Pablo Engel,
Gustavo Mourglia-Ettlin,
Francisco Lozano
Affiliations
Cristina Català
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain
María Velasco-de Andrés
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain
Alejandra Leyton-Pereira
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain
Sergi Casadó-Llombart
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain
Manuel Sáez Moya
Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Rebeca Gutiérrez-Cózar
Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Joaquín García-Luna
Área Inmunología, Facultad de Química/Facultad de Ciencias, DEPBIO/IQB, Universidad de la República, 11800 Montevideo, Uruguay
Marta Consuegra-Fernández
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain
Marcos Isamat
Sepsia Therapeutics S.L., 08908 L’Hospitalet de Llobregat, Spain
Fernando Aranda
Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain
Mario Martínez-Florensa
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain
Pablo Engel
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain; Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Gustavo Mourglia-Ettlin
Área Inmunología, Facultad de Química/Facultad de Ciencias, DEPBIO/IQB, Universidad de la República, 11800 Montevideo, Uruguay
Francisco Lozano
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain; Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain; Servei d’Immunologia, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, 08036 Barcelona, Spain; Corresponding author
Summary: CD6 is a lymphocyte-specific scavenger receptor expressed on adaptive (T) and innate (B1a, NK) immune cells, which is involved in both fine-tuning of lymphocyte activation/differentiation and recognition of bacterial-associated molecular patterns (i.e., lipopolysaccharide). However, evidence on CD6’s role in the physiological response to bacterial infection was missing. Our results show that induction of monobacterial and polymicrobial sepsis in Cd6−/− mice results in lower survival rates and increased bacterial loads and pro-inflammatory cytokine levels. Steady state analyses of Cd6−/− mice show decreased levels of natural polyreactive antibodies, concomitant with decreased cell counts of spleen B1a and marginal zone B cells. Adoptive transfer of wild-type B cells and mouse serum, as well as a polyreactive monoclonal antibody improve Cd6−/− mouse survival rates post-sepsis. These findings support a nonredundant role for CD6 in the early response against bacterial infection, through homeostatic expansion and functionality of innate-related immune cells.