Mannose-binding lectin deficiency influences innate and antigen-presenting functions of blood myeloid dendritic cells

Dean, Melinda M., Flower, Robert L., Eisen, Damon P., Minchinton, Robyn M., Hart, Derek N.J., and Vuckovic, Slavica (2011) Mannose-binding lectin deficiency influences innate and antigen-presenting functions of blood myeloid dendritic cells. Immunology, 132 (2). pp. 296-305.

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Abstract

Mannose-binding lectin (MBL) is a serum lectin that plays a significant role in innate host defence. Individuals with mutations in exon 1 of the MBL2 gene have reduced MBL ligand binding and complement activation function and increased incidence of infection. We proposed that, during infection, MBL deficiency may impact on dendritic cell (DC) function. We analysed the blood myeloid DC (MDC) surface phenotype, inflammatory cytokine production and antigen-presenting capacity in MBL-deficient (MBL-D) individuals and MBL-sufficient (MBL-S) individuals using whole blood culture supplemented with zymosan (Zy) or MBL-opsonized zymosan (MBL-Zy) as a model of infection. Zy-stimulated MDCs from MBL-D individuals had significantly increased production of interleukin (IL)-6 and tumour necrosis factor (TNF)-α. Stimulation with MBL-Zy significantly decreased IL-6 production by MDCs from MBL-D, but had no effect on TNF-α production. MDCs from both MBL-S and MBL-D individuals up-regulated expression of the activation molecule CD83, and down-regulated expression of homing (CXCR4), adhesion (CD62L, CD49d) and costimulatory (CD40, CD86) molecules in response to Zy and MBL-Zy. MDC from both MBL-D and MBL-S individuals induced proliferation of allogeneic (allo) T cells following Zy or MBL-Zy stimulation; however, MBL-D individuals demonstrated a reduced capacity to induce effector allo-T cells. These data indicate that MBL deficiency is associated with unique functional characteristics of pathogen-stimulated blood MDCs manifested by increased production of IL-6, combined with a poor capacity to induce effector allo-T-cell responses. In MBL-D individuals, these functional features of blood MDCs may influence their ability to mount an immune response.

Item ID: 52214
Item Type: Article (Research - C1)
ISSN: 1365-2567
Keywords: cytokines, dendritic cells, innate immunity, Interleukin-6, mannose-binding lectin
Date Deposited: 30 Jan 2018 02:30
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 80%
16 STUDIES IN HUMAN SOCIETY > 1605 Policy and Administration > 160508 Health Policy @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 80%
92 HEALTH > 9202 Health and Support Services > 920207 Health Policy Evaluation @ 20%
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