Bellanger Anne-Pauline, Pallandre Jean-René, Borg Christophe, Loeffert Sophie, Gbaguidi-Haore Houssein, Millon Laurence
University of Franche-Comté, Besançon, France.
Clin Vaccine Immunol. 2013 Aug;20(8):1133-42. doi: 10.1128/CVI.00043-13. Epub 2013 May 29.
Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula [actinomycetes], Mycobacterium immunogenum [mycobacteria], and Wallemia sebi and Eurotium amstelodami [filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR). E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than did W. sebi-exposed (WS), S. rectivirgula-exposed (SR), or M. immunogenum-exposed (MI) MoDCs (P < 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4(+) T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested.
过敏性肺炎（HP）是一种免疫过敏性疾病，其特征是主要由分泌炎性细胞因子的淋巴细胞组成的显著间质浸润。已知树突状细胞（DCs）在淋巴细胞反应中起关键作用。然而，它们与引起HP的微生物之间的相互作用尚未阐明。本研究旨在调查人单核细胞衍生的DCs（MoDCs）与四种性质不同的微生物（直丝糖多孢菌[放线菌]、免疫分枝杆菌[分枝杆菌]、西氏瓦勒霉菌和阿姆斯特丹散囊菌[丝状真菌]）之间的初始相互作用，这些微生物都与HP有关。我们的目标是确定MoDCs与HP病原体之间的相互作用，并确定所产生的免疫反应是否因所测试的微生物提取物而异。通过共刺激分子表达的增加和上清液中细胞因子水平来测量MoDCs的表型活化。通过MoDCs在混合淋巴细胞反应（MLR）中诱导淋巴细胞增殖和分化的能力来测量MoDCs的功能活化。暴露于阿姆斯特丹散囊菌（EA）的MoDCs比暴露于西氏瓦勒霉菌（WS）、直丝糖多孢菌（SR）或免疫分枝杆菌（MI）的MoDCs表达更高百分比的共刺激分子（P < 0.05，Wilcoxon符号秩检验）。EA-MoDCs、WS-MoDCs、SR-MoDCs和MI-MoDCs诱导CD4(+) T细胞增殖和Th1极化的免疫反应。本研究提供了证据，表明尽管最初观察到暴露于丝状真菌的MoDCs和暴露于细菌的MoDCs之间存在差异，但无论所测试的微生物提取物如何，DCs最终都会促进Th1反应。
