Human immature monocyte-derived dendritic cells produce and secrete -defensins 1 3

University of Barcelona, Barcino, Catalonia, Spain
Journal of Leukocyte Biology (Impact Factor: 4.29). 12/2007; 82(5):1143-6. DOI: 10.1189/jlb.0507295
Source: PubMed


Defensins are effector molecules of the innate immunity with a broad antimicrobial spectrum, including HIV. They also link innate and adaptive immunity, displaying chemotactic activity for monocytes, T cells, and dendritic cells (DCs). alpha-Defensins 1-3 are mainly produced by neutrophils, but their production by other leukocyte subsets has also been reported. Herein, we studied whether monocyte-derived DCs (MDDCs), which are regarded as a model for myeloid DCs, produce alpha-defensins 1-3. We found that immature MDDCs (imMDDCs) produce alpha-defensins 1-3 mRNA, but this production is undetectable or barely detectable following 48 h of maturation with the proinflammatory cytokine cocktail (IL-1beta+IL-6+TNF-alpha) or LPS. It is surprising that alpha-defensins 1-3 production was up-regulated when exposed to each one of the proinflammatory cytokines alone, especially IL-1beta. alpha-Defensins 1-3 produced by imMDDCs were mainly secreted peptides. Production and secretion of alpha-defensins 1-3 by imMDDCs can have biological relevance for the antigen processing of pathogens and can contribute to understanding differences in susceptibility to infections, an issue of special interest in the field of HIV infection.

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    • "natural killer cells and T lymphocyte subsets and act as immunomodulatory factors regulating acute inflammation, phagocytosis, cell migration/maturation and cytokine secretion (Klotman and Chang, 2006; Rodriguez-Garcia et al., 2007; Selsted and Ouellette, 2005). DEFA4 inhibits synthesis of anti-inflammatory glucocorticoids known to have significant influence on developing synaptic structure and function in the adult brain (Owen et al., 2005). "
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    • "Similar to sPLA2, NP defensin 3 exhibits antimicrobial activity as well as other immune modulatory roles [99, 115, 116]. Normal colonic expression of alpha defensins is low [96, 97], but expression is induced during inflammation [96, 97, 117, 118], potentially by the proinflammatory cytokines IL-1β, TNF-α, and IL-6 [119]. Recently, increased levels of human neutrophil (HNP) defensins 1–3 were identified in individuals with colorectal tumors [120–122] as well as in the serum and colon from patients with active IBD [117], indicating that alpha defensins may be a plausible and early biomarker for gastrointestinal disease. "
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