Wilson C B, Haas J E
J Clin Invest. 1984 Jun;73(6):1606-16. doi: 10.1172/JCI111367.
Mononuclear phagocytes, particularly macrophages (M phi) that have been activated by lymphokines, are the principal defense against intracellular pathogens such as Toxoplasma gondii. To determine reasons for the newborns' susceptibility to Toxoplasma infection, we compared: the interaction of Toxoplasma with newborns' mononuclear phagocytes (blood monocytes and two types of newborn M phi, those derived from blood monocytes or from placental tissue) with adults' blood monocytes and monocyte-derived M phi and the production of M phi-activating lymphokines (MAF) by Concanavalin A (ConA)-stimulated newborn and adult blood mononuclear cells (MC). Newborn and adult monocytes killed Toxoplasma with equal efficiency. Similarly, survival and replication of Toxoplasma were comparable in control newborn and adult M phi. Exposure to adult ConA supernatants significantly decreased the survival and replication of Toxoplasma both in adult and newborn M phi. In contrast, exposure to cord blood ConA supernatants failed to affect the survival or the replication of Toxoplasma in newborn M phi and decreased the replication but not the survival of Toxoplasma in adult M phi. Exposure to ConA supernatants of peripheral blood MC from 2-5-d old newborns failed to affect survival or replication of Toxoplasma in newborn or adult M phi. Thus, both generation of MAF by newborn blood MC and response to newborn MAF by newborn M phi were impaired. Generation of MAF by adult blood mononuclear cells was not inhibited by cord blood MC nor was generation of MAF by cord blood MC increased by depletion of OKT8 antibody-binding cells, by depletion of adherent cells with or without addition of adult adherent cells, or by addition of indomethacin. Depletion of OKT4 antibody-binding cells abrogated the generation of MAF both by adult and cord blood MC. The activity of adult ConA supernatants was abrogated by dialysis at pH 2 or by addition of anti-gamma-interferon but not anti-alpha-interferon antibody. However, the correlation between antiviral interferon activity and anti-Toxoplasma activity was weak (r = 0.40). Enhanced M phi anti-Toxoplasma activity was not associated with detectably enhanced superoxide anion generation, nitroblue tetrazolium reduction, or phagolysosome fusion, and was not inhibited by catalase, superoxide dismutase, or mannitol. These results indicate that generation of and response to MAF is decreased in cells from human newborns and that gamma-interferon may be the major MAF under these conditions.
单核吞噬细胞，尤其是被淋巴因子激活的巨噬细胞（M phi），是抵御细胞内病原体如弓形虫的主要防线。为了确定新生儿易患弓形虫感染的原因，我们比较了：弓形虫与新生儿单核吞噬细胞（血液单核细胞以及两种新生儿M phi，即源自血液单核细胞或胎盘组织的M phi）、成人血液单核细胞和单核细胞衍生的M phi之间的相互作用，以及伴刀豆球蛋白A（ConA）刺激的新生儿和成人血液单核细胞（MC）产生M phi激活淋巴因子（MAF）的情况。新生儿和成人的单核细胞杀灭弓形虫的效率相同。同样，在对照的新生儿和成人M phi中，弓形虫的存活和增殖情况相当。暴露于成人ConA上清液显著降低了成人和新生儿M phi中弓形虫的存活和增殖。相反，暴露于脐血ConA上清液未能影响新生儿M phi中弓形虫的存活或增殖，且降低了成人M phi中弓形虫的增殖但未影响其存活。暴露于2 - 5日龄新生儿外周血MC的ConA上清液未能影响新生儿或成人M phi中弓形虫的存活或增殖。因此，新生儿血液MC产生MAF以及新生儿M phi对新生儿MAF的反应均受损。成人血液单核细胞产生MAF不受脐血MC的抑制，脐血MC产生MAF也不会因去除OKT8抗体结合细胞、去除贴壁细胞（无论是否添加成人贴壁细胞）或添加消炎痛而增加。去除OKT4抗体结合细胞可消除成人和脐血MC产生MAF的能力。成人ConA上清液的活性可通过在pH 2下透析或添加抗γ干扰素而非抗α干扰素抗体来消除。然而，抗病毒干扰素活性与抗弓形虫活性之间的相关性较弱（r = 0.40）。增强的M phi抗弓形虫活性与可检测到的超氧阴离子生成增强、硝基蓝四氮唑还原增强或吞噬溶酶体融合增强无关，且不受过氧化氢酶、超氧化物歧化酶或甘露醇的抑制。这些结果表明，人类新生儿细胞中MAF的产生和反应降低，并且在这些条件下γ干扰素可能是主要的MAF。
