title: Surfactant protein D induces immune quiescence and apoptosis of mitogen-activated peripheral blood mononuclear cells.
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.
authors.affiliation: Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Hrishikesh
authors.initials: H
authors.lastname: Pandit
authors.affiliation: Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Gargi
authors.initials: G
authors.lastname: Thakur
authors.affiliation: Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Aghila Rani
authors.initials: AR
authors.lastname: Koippallil Gopalakrishnan
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, College of Health and Life Sciences, Brunel University, London, Uxbridge, UB8 3PH, United Kingdom.
authors.forename: Eswari
authors.initials: E
authors.lastname: Dodagatta-Marri
authors.affiliation: Department of Clinical Research, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Anushree
authors.initials: A
authors.lastname: Patil
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, College of Health and Life Sciences, Brunel University, London, Uxbridge, UB8 3PH, United Kingdom.
authors.forename: Uday
authors.initials: U
authors.lastname: Kishore
authors.affiliation: Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, India. Electronic address: taruna_m@hotmail.com.
authors.forename: Taruna
authors.initials: T
authors.lastname: Madan
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D061251:Primary Cell Culture; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039521:CD11c Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D007371:Interferon-gamma; D016753:Interleukin-10; D020381:Interleukin-17; D007376:Interleukin-2; D015847:Interleukin-4; D015850:Interleukin-6; D037181:Lectins, C-Type; D010835:Phytohemagglutinins; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C556706:CTLA4 protein, human; C508609:IL10 protein, human; C508717:IL17A protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human
keywords: CTLA4; Inflammation; Lymphocytes; Monocytes; PBMC; Surfactant protein D