Neutrophil Granulocyte–committed Cells Can Be Driven to Acquire Dendritic Cell Characteristics

Abstract

Polymorphonuclear granulocytes (PMNs) are thought to fulfill their role in host defense primarily via phagocytosis and release of cytotoxic compounds and to be inefficient in antigen presentation and stimulation of specific T cells. Dendritic cells (DCs), in contrast, are potent antigen-presenting cells with the unique capacity to initiate primary immune responses. We demonstrate here that highly purified lactoferrin-positive immediate precursors of end-stage neutrophilic PMN (PMNp) can be reverted in their functional maturation program and driven to acquire characteristic DC features. Upon culture with the cytokine combination granulocyte/macrophage colony-stimulating factor plus interleukin 4 plus tumor necrosis factor α, they develop DC morphology and acquire molecular features characteristic for DCs. These molecular changes include neo-expression of the DC-associated surface molecules cluster of differentiation (CD)1a, CD1b, CD1c, human leukocyte antigen (HLA)-DR, HLA-DQ, CD80, CD86, CD40, CD54, and CD5, and downregulation of CD15 and CD65s. Additional stimulation with CD40 ligand induces also expression of CD83 and upregulates CD80, CD86, and HLA-DR. The neutrophil-derived DCs are potent T cell stimulators in allogeneic, as well as autologous, mixed lymphocyte reactions (MLRs), whereas freshly isolated neutrophils are completely unable to do so. In addition, neutrophil-derived DCs are at least 10,000 times more efficient in presenting soluble antigen to autologous T cells when compared to freshly isolated monocytes. Also, in functional terms, these neutrophil-derived DCs thus closely resemble “classical” DC populations.

Reprogramming of human postmitotic neutrophils into macrophages by growth factors

“…Such a lineage switch may occur under specified conditions, such as inflammation, because GM-CSF, TNF-␣, IFN-␥, IL-4, and M-CSF are inflammatory cytokines. Oehler et al 46 demonstrate that neutrophil granulocytecommitted cells acquire dendritic cell features in the presence of GM-CSF, IL-4, and TNF-␣. Our results indicated that when CD15 ϩ CD14 Ϫ cells were cultured with GM-CSF, TNF-␣, IFN-␥, and IL-4, the resultant cells exhibited a partial appearance of macrophages.…”

Expression of dendritic cell markers on cultured neutrophils and its modulation by anti-apoptotic and pro-apoptotic compounds

“…Recent experimental data suggests that neutrophils have the potential to trans-differentiate into DCs (Oehler et al, 1998;Yamashiro et al, 2000;Iking-Konert et al, 2001a). Therefore, neutrophils appear to have different phenotypic characteristics depending on a variety of factors, including the survival duration.…”

“…Human peripheral blood and inflammatory neutrophils express functional B7-1-like molecules, and the expression of these molecules is upregulated by the neutrophils of patients with chronic inflammatory disease or Wegener's granulomatosis (Windhagen et al, 1999;Iking-Konert et al, 2001b. The in vitro generation of dendritic cell (DC)-like cells from immediate precursors of mature neutrophils (Oehler et al, 1998) or neutrophils from the peripheral blood using cytokines has also been reported (Yamashiro et al, 2000;IkingKonert et al, 2001a). Neutrophils and immature DCs co-localize during pathogenic challenge (van Gisbergen et al, 2005).…”

Neutrophile et immunité

“…Le neutrophile au repos exprime uniquement les molécules du CMH de classe I. Le neutrophile activé en présence d'IFN-γ, GM-CSF, TNF-α, IL-4 va se modifier et exprimer à sa surface le CMH de classe II, CD83, CD40 et CCR6 mais, de plus, les molécules de co-stimulation CD80 (B7-1) et CD86 (B7-2), critères définissant une cellule dendritique [22][23][24]. Certains neutrophiles au repos possèdent déjà, dans leur cytoplasme, ces molécules pré-stockées ; ils en possèdent éga-lement d'autres comme CD20, 21, 22, marqueurs de lymphocytes B [25].…”

“…La présentation antigénique par le neutrophile est efficace puisqu'il peut alors activer les lymphocytes T mis en présence du peptide antigénique par ce neutrophile, que ce soit un peptide conventionnel ou un superantigène [26][27][28]. Le neutrophile, devenu une cellule de type dendritique, semble être 10 000 fois plus efficace à pré-senter l'antigène qu'une cellule dendritique classique en provenance de monocytes [23]. Le neutrophile peut aussi présenter un antigène peptidique en utilisant la voie du CMH de classe I [29].…”