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The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression

Cellular & Molecular Immunology volume 11, pages 343–354 (2014)Cite this article

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.

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Acknowledgements

We would like to thank Dr Rosa Aligué (Cell Biology Unit of the University of Barcelona) and Dr. Jordi Vila (Department of Microbiology of the Hospital Clinic of Barcelona) for their kind help with microbial specimens. This study was supported by grants from the Spanish Ministerio de Economía y Competitividad (SAF2010-19717), Generalitat de Catalunya (2009SGR1101) and Instituto de Salud Carlos III (Spanish Network for Research in Infectious Diseases, REIPI, RD12/0015/0018). VGM is recipient of a fellowship from Ministerio de Economia y Competitividad (JCI-2010-06378). CE-F is recipient of a fellowship from Spanish Ministerio de Economía y Competitividad (BES-2008-005544).

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Author notes

  1. Vanesa G. Martinez and Cristina Escoda-Ferran: Authors contributed equally to this work.

Authors and Affiliations

  1. Grup d'Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Vanesa G. Martinez, Cristina Escoda-Ferran, Inês Tadeu Simões, Marc Orta Mascaró, Esther Carreras, Mario Martínez-Florensa & Francisco Lozano

  2. Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo

    Satoko Arai & Toru Miyazaki

  3. Hospital del Mar Medical Research Institute and Department of Immunology, Cancer Research Program, Hospital del Mar, Barcelona, Spain

    José Yelamos

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

    Francisco Lozano

  5. Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain

    Francisco Lozano

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  1. Vanesa G. Martinez
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Correspondence to Francisco Lozano.

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Martinez, V., Escoda-Ferran, C., Tadeu Simões, I. et al. The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression. Cell Mol Immunol 11, 343–354 (2014). https://doi.org/10.1038/cmi.2014.12

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