Bhardwaj N, Nash T W, Horwitz M A
J Immunol. 1986 Oct 15;137(8):2662-9.
We have examined the interaction between interferon-gamma (IFN-gamma)-activated human monocytes and Legionella pneumophila, the agent of Legionnaires' disease. Human monocytes activated with human recombinant IFN-gamma inhibit the intracellular multiplication of L. pneumophila. The degree of inhibition is proportional to the concentration of IFN-gamma, and maximal inhibition consistently occurs with greater than or equal to 2 micrograms/ml. Monoclonal anti-IFN-gamma antibody completely neutralizes the capacity of IFN-gamma to activate monocytes. Monocytes infected 24 hr after explantation maximally inhibit L. pneumophila multiplication if treated with IFN-gamma before infection or up to 2 hr after infection; treatment 6 hr or more after infection results in submaximal inhibition. Monocytes infected 48 hr after explantation inhibit L. pneumophila multiplication maximally if treated with IFN-gamma up to 12 hr before infection, but submaximally if treated at the time of infection. Once activated, monocytes inhibit L. pneumophila multiplication in the absence of IFN-gamma in the culture. Strikingly, monocytes maximally inhibit L. pneumophila multiplication after treatment with IFN-gamma for as briefly as 1 hr before infection. In the absence of anti-L. pneumophila antibody, neither IFN-gamma-activated monocytes nor nonactivated monocytes kill L. pneumophila. In the presence of specific antibody and complement, IFN-gamma-activated monocytes kill a proportion (0.5 log) of an inoculum but not more than nonactivated monocytes. L. pneumophila forms a specialized phagosome in IFN-gamma-activated monocytes that does not differ ultrastructurally from the L. pneumophila phagosome in nonactivated monocytes. These results demonstrate that IFN-gamma can activate human monocytes to exert a potent antimicrobial effect against a highly virulent intracellular bacterial pathogen. These findings extend previous observations on interactions between activated mononuclear phagocytes and L. pneumophila, and additionally support the hypothesis that cell-mediated immunity plays a major role in host defense against L. pneumophila.
我们研究了γ-干扰素（IFN-γ）激活的人单核细胞与退伍军人病病原体嗜肺军团菌之间的相互作用。用人重组IFN-γ激活的人单核细胞可抑制嗜肺军团菌在细胞内的增殖。抑制程度与IFN-γ的浓度成正比，当浓度大于或等于2微克/毫升时，始终会出现最大抑制作用。单克隆抗IFN-γ抗体可完全中和IFN-γ激活单核细胞的能力。接种后24小时感染的单核细胞，如果在感染前或感染后2小时内用IFN-γ处理，对嗜肺军团菌增殖的抑制作用最大；感染后6小时或更长时间处理则导致抑制作用不充分。接种后48小时感染的单核细胞，如果在感染前12小时内用IFN-γ处理，对嗜肺军团菌增殖的抑制作用最大，但在感染时处理则抑制作用不充分。一旦被激活，单核细胞在培养物中无IFN-γ的情况下也能抑制嗜肺军团菌的增殖。引人注目的是，单核细胞在感染前用IFN-γ处理仅1小时后，对嗜肺军团菌增殖的抑制作用最大。在没有抗嗜肺军团菌抗体的情况下，IFN-γ激活的单核细胞和未激活的单核细胞均不能杀死嗜肺军团菌。在存在特异性抗体和补体的情况下，IFN-γ激活的单核细胞可杀死一定比例（0.5个对数）的接种物，但不超过未激活的单核细胞。嗜肺军团菌在IFN-γ激活的单核细胞中形成一种特殊的吞噬体，其超微结构与未激活的单核细胞中的嗜肺军团菌吞噬体没有差异。这些结果表明，IFN-γ可激活人单核细胞，对高毒力的细胞内细菌病原体发挥强大的抗菌作用。这些发现扩展了先前关于激活的单核吞噬细胞与嗜肺军团菌之间相互作用的观察结果，并进一步支持了细胞介导的免疫在宿主抵御嗜肺军团菌防御中起主要作用的假说。
