title: The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression.
abstract: Apoptosis inhibitor of macrophages (AIMs), a homologue of human Spα, is a mouse soluble member of the scavenger receptor cysteine-rich superfamily (SRCR-SF). This family integrates a group of proteins expressed by innate and adaptive immune cells for which no unifying function has yet been described. Pleiotropic functions have been ascribed to AIM, from viability support in lymphocytes during thymic selection to lipid metabolism and anti-inflammatory effects in autoimmune pathologies. In the present report, the pathogen binding properties of AIM have been explored. By using a recombinant form of AIM (rAIM) expressed in mammalian cells, it is shown that this protein is able to bind and aggregate Gram-positive and Gram-negative bacteria, as well as pathogenic and saprophytic fungal species. Importantly, endogenous AIM from mouse serum also binds to microorganisms and secretion of AIM was rapidly induced in mouse spleen macrophages following exposure to conserved microbial cell wall components. Cytokine release induced by well-known bacterial and fungal Toll-like receptor (TLR) ligands on mouse splenocytes was also inhibited in the presence of rAIM. Furthermore, mouse models of pathogen-associated molecular patterns (PAMPs)-induced septic shock of bacterial and fungal origin showed that serum AIM levels changed in a time-dependent manner. Altogether, these data suggest that AIM plays a general homeostatic role by supporting innate humoral defense during pathogen aggression.
authors.affiliation: Grup d'Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Vanesa G
authors.initials: VG
authors.lastname: Martinez
authors.affiliation: Grup d'Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Escoda-Ferran
authors.affiliation: Grup d'Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Inês
authors.initials: I
authors.lastname: Tadeu Simões
authors.affiliation: Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo.
authors.forename: Satoko
authors.initials: S
authors.lastname: Arai
authors.affiliation: Grup d'Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Orta Mascaró
authors.affiliation: Grup d'Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Carreras
authors.affiliation: Grup d'Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Martínez-Florensa
authors.affiliation: Cancer Research Program, Hospital del Mar Medical Research Institute and Department of Immunology, Hospital del Mar, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Yelamos
authors.affiliation: Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo.
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: 1] Grup d'Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain [2] Servei d'Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic Barcelona, Barcelona, Spain [3] Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Lozano
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D002473:Cell Wall / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005658:Fungi / Q000472:pathogenicity / Q000502:physiology*; D005786:Gene Expression Regulation; D006094:Gram-Positive Bacteria / Q000472:pathogenicity / Q000502:physiology*; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012772:Shock, Septic / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C492821:CD5L protein, human; C117272:Cd5l protein, mouse; D016207:Cytokines; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B