Gussmann Kathrin, Kirschnek Susanne, von Loewenich Friederike D
Institute of Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, D-79104, Freiburg, Germany.
Department of Medical Microbiology and Hygiene, University of Mainz, Obere Zahlbacherstrasse 67, D-55131, Mainz, Germany.
Parasit Vectors. 2017 Jul 12;10(1):329. doi: 10.1186/s13071-017-2274-6.
Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that is transmitted by ticks of the Ixodes ricinus complex. It replicates in neutrophils and elicits febrile disease in humans and animals. Because of its striking tropism for neutrophils, A. phagocytophilum has been used as a model organism to study the immune response against obligate intracellular pathogens. In mice, the control of A. phagocytophilum in the early phase of infection is dependent on natural killer cell-derived interferon-γ (IFN-γ). In contrast, the final elimination strictly requires CD4 T-cells. It is a matter of debate, whether neutrophils serve only as host cells or as killer cells as well.
To study this, we used in vitro generated murine neutrophils with defects in major antimicrobial molecules such as NADPH-oxidase (gp91), myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS). However, bacterial growth in gene-deficient neutrophils was comparable to that in wild-type cells. Whereas gp91 and MPO expression remained unchanged, the infection led to an induction of iNOS. In neutrophils stimulated with IFN-γ, bacterial growth was significantly impaired, and iNOS was induced. However, the antibacterial effect of IFN-γ was still seen in iNOS neutrophils.
Thus, murine in vitro generated neutrophils stimulated with IFN-γ seem to act as killer cells by an iNOS-independent mechanism.
嗜吞噬细胞无形体是一种革兰氏阴性专性细胞内细菌，由蓖麻硬蜱属蜱传播。它在中性粒细胞中复制，并在人和动物中引发发热性疾病。由于其对中性粒细胞具有显著的嗜性，嗜吞噬细胞无形体已被用作研究针对专性细胞内病原体免疫反应的模式生物。在小鼠中，感染早期对嗜吞噬细胞无形体的控制依赖于自然杀伤细胞衍生的干扰素-γ（IFN-γ）。相比之下，最终清除则严格需要CD4 T细胞。中性粒细胞仅仅作为宿主细胞还是也作为杀伤细胞，这是一个有争议的问题。
为了研究这一点，我们使用了体外生成的在主要抗菌分子如NADPH氧化酶（gp91）、髓过氧化物酶（MPO）和诱导型一氧化氮合酶（iNOS）方面存在缺陷的小鼠中性粒细胞。然而，基因缺陷的中性粒细胞中的细菌生长与野生型细胞中的相当。虽然gp91和MPO的表达保持不变，但感染导致了iNOS的诱导。在用IFN-γ刺激的中性粒细胞中，细菌生长显著受损，并且iNOS被诱导。然而，在iNOS缺陷的中性粒细胞中仍可看到IFN-γ的抗菌作用。
因此，体外生成的用IFN-γ刺激的小鼠中性粒细胞似乎通过一种不依赖iNOS的机制充当杀伤细胞。
