Characterization of Myeloid and Plasmacytoid Dendritic Cells in Human Lung

Abstract

Dendritic cells (DCs) are bone marrow-derived mononuclear cells that play a central role in the initiation of immune responses. Because human lung DCs have been incompletely characterized, we enumerated and phenotyped mononuclear cell populations from excess lung tissue obtained at surgery. Myeloid DCs (MDCs) were identified as CD1c+CD11c+CD14−HLA-DR+ cells and comprised ∼2% of low autofluorescent (LAF) mononuclear cells. Plasmacytoid DCs (PDCs) were characterized as CD123+CD11c−CD14−HLA-DR+ cells and comprised ∼1.0% of the LAF mononuclear cells. Cells enriched in MDCs expressed CD86, moderate CD80, and little CD40, but cells enriched in PDCs had little to no expression of these three costimulatory molecules. CD11c+CD14− lineage-negative (MDC-enriched) LAF cells were isolated and shown to be much more potent in stimulating an alloreaction than CD11c+CD14+ lineage-negative (monocyte-enriched) LAF cells. PDC-enriched cells were more capable of responding to a TLR-7 agonist by secreting IFN-α than MDC-enriched cells. MDC-enriched cells were either CD123+ or CD123−, but both subsets secreted cytokines and chemokines typical of MDC upon stimulation with a TLR-4 agonist and both subsets failed to secrete IFN-α upon stimulation with a TLR-7 agonist. By immunohistochemistry, we identified MDCs throughout different anatomical locations of the lung. However, our method did not allow the localization of PDCs with certainty. In conclusion, in the human lung MDCs were twice as numerous and expressed higher levels of costimulatory molecules than PDCs. Our data suggest that both lung DC subsets exert distinct immune modulatory functions.

Airway Eosinophils: Allergic Inflammation Recruited Professional Antigen-Presenting Cells

“…Our findings do not diminish roles of natively resident lung and airway DCs and other cells as APCs (10,28,30), but rather establish that eosinophils, cells of the innate immune system, when recruited into sites of allergic inflammation may have additional roles as "inflammatory" APCs in modulating ongoing adaptive T cell-mediated immune responses. In the context of usually chronic, allergic inflammation that accompanies nasal polyposis, allergic rhinoconjunctivitis, and asthma, airway eosinophils have the capacity to provide additional functions as APCs.…”

“…The lungs natively contain a range of cells capable of being induced to function as professional APCs, including plasmacytoid DCs, types of CD11c ϩ myeloid DCs, B cells, and macrophages (28,30). Unlike the gastrointestinal tract where eosinophils normally home and might be exposed to gut-derived Ags (26), eosinophils are not abundant in the normal lungs or airways (26,27).…”

Dendritic Cells in the Kidney

“…Similar to DC in other nonlymphoid organs, [33][34][35] rDC constitute a heterogeneous population of bone marrow-derived hematopoietic cells that, unlike DC that function solely within lymphoid tissues (most of the DC in the thymus and spleen and approximately half of the DC in lymph nodes), serve as sentinels within the kidney before trafficking to lymphoid organs. [13][14][15][16][17][18] Because of the plasticity of FLT3 ϩ common myeloid and common lymphoid DC precursors to generate all DC subsets, 16 local trophic cues rather than the availability of DC precursors probably determine the constituency of rDC at steady state.…”

HIV-Associated Bacterial Pneumonia

“…In this setting, pulmonary plasmacytoid DCs interact with HIV via CD4,resulting in internalization of the virus. In the cell cytoplasm, viral RNA is recognized by intracellular pathogen recognition receptors known as Toll-like receptors (TLRs)-7 and -9 [20][21][22][23], and possibly by the more recently described cytoplasmic pathogen nucleic acid sensors [24]. This leads, in turn, to excessive and sustained production of: i) type I interferon (IFN); ii) the tryptophan catabolizing enzyme, indoleamine 2,3-dioxygenase; and iii) the cytokine, transforming growth factor β (TGF-β), all of which contribute to immune dysfunction [20,[25][26][27][28][29][30][31][32][33].…”