SELECTIVE PROTECTION AGAINST CONIDIA BY MONONUCLEAR AND AGAINST MYCELIA BY POLYMORPHONUCLEAR PHAGOCYTES IN RESISTANCE TO ASPERGILLUS - OBSERVATIONS ON THESE 2 LINES OF DEFENSE INVIVO AND INVITRO WITH HUMAN AND MOUSE PHAGOCYTES
SELECTIVE PROTECTION AGAINST CONIDIA BY MONONUCLEAR AND AGAINST MYCELIA BY POLYMORPHONUCLEAR PHAGOCYTES IN RESISTANCE TO ASPERGILLUS - OBSERVATIONS ON THESE 2 LINES OF DEFENSE INVIVO AND INVITRO WITH HUMAN AND MOUSE PHAGOCYTES
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DOI：
10.1172/jci110489
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发表时间：
1982-01-01
影响因子：
15.9
通讯作者：
BRAUDE, A
中科院分区：
文献类型：
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作者：
SCHAFFNER, A;DOUGLAS, H;BRAUDE, A
通过比较天然免疫与A.在体外，人或小鼠吞噬细胞对AF的作用，阐明了2条连续的抗AF的防线。第一道防线是由巨噬细胞形成的，针对孢子。巨噬细胞在体外阻止孢子萌发并杀死孢子，在体内迅速根除分生孢子，甚至在无胸腺和无胸腺小鼠中也是如此。其次是嗜中性粒细胞（PMN），它对AF的菌丝形式具有保护作用。正常小鼠（但不是贫血小鼠）停止菌丝生长并根除菌丝体。单独作用的任一防御线保护小鼠免受高攻击剂量。只有当RES和PMN都受损时，自然免疫才会崩溃。因此，高剂量的可的松和中性粒细胞减少症显然是侵袭性曲霉病的主要危险因素。可的松在体内抑制小鼠巨噬细胞的杀分生孢子活性，在体外抑制人或小鼠单核吞噬细胞的杀分生孢子活性。可的松直接破坏这第一道防线，而不是通过T淋巴细胞或其他系统的影响改变巨噬细胞的功能，如在无胸腺小鼠和体外所示。小鼠每日高剂量的可的松减少了PMN的动员，因此第二道防线也受到损害。因此，可的松可以自行分解自然抵抗力。只有当第一道防线被高激发剂量、不能被巨噬细胞杀死的活化孢子或可的松抑制巨噬细胞的杀分生孢子活性所压倒时，骨髓抑制才使小鼠易感。因此，宿主可以调用2个独立的吞噬细胞系，形成针对曲霉菌的分级防御系统。这些防线在没有特异性免疫反应的情况下发挥作用，这在控制和消除这种真菌方面似乎是多余的。
By comparing natural immunity to A. fumigatus (AF) in vivo with the action of human or mouse phagocytes against AF in vitro, 2 sequential lines of defense against AF were delineated. The 1st line of defense was formed by macrophages and directed against spores. Macrophages prevented germination and killed spores in vitro and rapidly eradicated conidia in vivo, even in neutropenic and athymic mice. The 2nd was the neutrophilic granulocyte (PMN), which protected against the hyphal form of AF. Human and mouse PMN killed mycelia in vitro. Normal, but not neutropenic mice, stopped hyphal growth and eradicated mycelia. Either line of defense acting alone protected mice from high challenge doses. Natural immunity collapsed only when both the RES and PMN were impaired. Thus, high doses of cortisone and neutropenia evidently are the main risk factors for invasive aspergillosis. Cortisone inhibited the conidiacidal activity of mouse macrophages in vivo and of human or mouse mononuclear phagocytes in vitro. Cortisone damaged this 1st line of defense directly and not through the influence of T lymphocytes or other systems modifying macrophage function as shown in athymic mice and in vitro. Daily high doses of cortisone in mice reduced the mobilization of PMN so that the 2nd line of defense was also impaired. Thus, cortisone can break down natural resistance on its own. Myelosuppression rendered mice susceptible only when the 1st line of defense was overpowered by high challenge doses, by activated spores that cannot be killed by macrophages or by cortisone suppression of the conidiacidal activity of macrophages. The host, thus, can call upon 2 independent phagocytic cell lines that form graded defense systems against Aspergillus. These lines of defense function in the absence of a specific immune response, which seems superfluous in the control and elimination of this fungus.