Surfactant protein D induces immune quiescence and apoptosis of mitogen-activated peripheral blood mononuclear cells

• Published in: Immunobiology (1979) 2016-02, Vol.221 (2), p.310-322
• Main Authors: Pandit, Hrishikesh, Thakur, Gargi, Koippallil Gopalakrishnan, Aghila Rani, Dodagatta-Marri, Eswari, Patil, Anushree, Kishore, Uday, Madan, Taruna
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Allergy and Immunology; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; Apoptosis - drug effects; Apoptosis - immunology; CD11c Antigen - genetics; CD11c Antigen - immunology; CD28 Antigens - genetics; CD28 Antigens - immunology; Cell Lineage - drug effects; Cell Lineage - immunology; CTLA-4 Antigen - genetics; CTLA-4 Antigen - immunology; CTLA4; Gene Expression Regulation - drug effects; Humans; Inflammation; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-17 - genetics; Interleukin-17 - immunology; Interleukin-2 - genetics; Interleukin-2 - immunology; Interleukin-4 - genetics; Interleukin-4 - immunology; Interleukin-6 - genetics; Interleukin-6 - immunology; Lectins, C-Type - genetics; Lectins, C-Type - immunology; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphocytes; Monocytes; PBMC; Phytohemagglutinins - pharmacology; Primary Cell Culture; Protein Structure, Tertiary; Pulmonary Surfactant-Associated Protein D - pharmacology; Recombinant Proteins - pharmacology; Signal Transduction; Surfactant protein D; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2015.10.004

Abstract Surfactant protein D (SP-D) is an integral molecule of the innate immunity secreted by epithelial cells lining the mucosal surfaces. The C-type lectin domain of SP-D performs pattern recognition functions while it binds to putative receptors on immune cells to modify cellular functions. Activation of immune cells and increased serum SP-D is observed in a range of patho-physiological conditions including infections. We speculated if SP-D can modulate systemic immune response via direct interaction with activated PBMCs. In this study, we examined interaction of a recombinant fragment of human SP-D (rhSP-D) on PHA-activated PBMCs. We report a significant downregulation of activation receptors such as TLR2, TLR4, CD11c and CD69 upon rhSP-D treatment. rhSP-D inhibited production of Th1 (TNF-α and IFN-γ) and Th17 (IL-17A) cytokines along with IL-6. Interestingly, levels of IL-2, Th2 (IL-4) and regulatory (IL-10 and TGF-β) cytokines remained unaltered. Analysis of co-stimulatory CD28 and co-inhibitory CTLA4 receptors along with their ligands CD80 and CD86 revealed a selective up-regulation of CTLA4 in the lymphocyte subset. rhSP-D induced apoptosis in the activated but not in non-activated lymphocytes. Blockade of CTLA4 inhibited rhSP-D mediated apoptosis of activated lymphocytes, confirming involvement of CTLA4. We conclude that SP-D restores immune homeostasis. It regulates expression of immunomodulatory receptors and cytokines, which is followed by induction of apoptosis in activated lymphocytes. These findings suggest a critical role of SP-D in immune surveillance against activated immune cells.