Deficient Complement Opsonization Impairs Mycobacterium avium Killing by Neutrophils in Cystic Fibrosis.
Deficient Complement Opsonization Impairs Mycobacterium avium Killing by Neutrophils in Cystic Fibrosis.
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DOI：
10.1128/spectrum.03279-22
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发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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非结核分枝杆菌 (NTM)，包括鸟分枝杆菌，是囊性纤维化 (CF) 的临床重要病原体。对鸟分枝杆菌的先天免疫反应仍不完全清楚。我们评估了补体调理作用在中性粒细胞介导的鸟分枝杆菌杀伤中的作用。使用来自健康供体 (HD) 和 CF 患者 (pwCF) 的中性粒细胞进行杀伤测定。鸟分枝杆菌的临床分离株用 HD 或 pwCF 的血浆进行调理，这些血浆是完整的或经过热处理以灭活补体。 HD中性粒细胞对用完整HD血浆调理的鸟分枝杆菌具有杀伤活性，并且当用热灭活的HD血浆调理鸟分枝杆菌时，杀伤力显着降低。当用 HD 血浆调理时，CF 中性粒细胞对鸟分枝杆菌具有杀伤活性，这与 HD 中性粒细胞没有不同。当用 pwCF 的完整血浆调理时，HD 中性粒细胞对鸟分枝杆菌的杀伤显着减少。用 C3 耗尽的血清或 IgM 耗尽的血浆调理鸟分枝杆菌导致杀灭率显着减少。与未感染 NTM 的 pwCF 相比，感染 NTM 的 pwCF 中血浆 C3 水平升高。这些研究表明，在 HD 血浆因子（包括 C3 和 IgM）存在下进行调理时，人类中性粒细胞可有效杀死鸟分枝杆菌。当细菌被 pwCF 血浆调理时，杀灭效率显着降低。这表明调理作用在嗜中性粒细胞杀死鸟分枝杆菌中的新作用以及补体调理作用的缺陷作为CF中鸟分枝杆菌杀伤受损的机制。重要性 鸟分枝杆菌是非结核分枝杆菌 (NTM) 细菌中的一员，可导致某些人群（包括囊性纤维化 (CF) 患者）肺部疾病。 NTM 感染很难诊断，治疗起来也更加困难。本研究调查了 CF 中免疫系统如何应对鸟分枝杆菌感染。我们发现，中性粒细胞是 CF 患者肺部最丰富的免疫细胞，无论是否患有 CF，都可以有效杀死鸟分枝杆菌。此过程还需要免疫反应的另一个组成部分，称为补体系统。与没有 NTM 感染史的 CF 患者相比，有 NTM 病史的患者补体蛋白水平发生了变化。这些结果增加了我们对免疫系统如何响应鸟分枝杆菌的理解，这有助于为更好的诊断和治疗策略铺平道路。
Nontuberculous mycobacteria (NTM), including Mycobacterium avium, are clinically important pathogens in cystic fibrosis (CF). The innate immune response to M. avium remains incompletely understood. We evaluated the role of complement opsonization in neutrophil-mediated killing of M. avium. Killing assays were performed using neutrophils from healthy donors (HDs) and persons with CF (pwCF). Clinical isolates of M. avium were opsonized with plasma from HDs or pwCF, which was intact or heat-treated to inactivate complement. HD neutrophils had killing activity against M. avium opsonized with intact HD plasma and killing was significantly reduced when M. avium was opsonized with heat-inactivated HD plasma. When opsonized with HD plasma, CF neutrophils had killing activity against M. avium that was not different than HD neutrophils. When opsonized with intact plasma from pwCF, HD neutrophil killing of M. avium was significantly reduced. Opsonization of M. avium with C3-depleted serum or IgM-depleted plasma resulted in significantly reduced killing. Plasma C3 levels were elevated in pwCF with NTM infection compared to pwCF without NTM infection. These studies demonstrate that human neutrophils efficiently kill M. avium when opsonized in the presence of plasma factors from HD that include C3 and IgM. Killing efficiency is significantly lower when the bacteria are opsonized with plasma from pwCF. This indicates a novel role for opsonization in neutrophil killing of M. avium and a deficiency in complement opsonization as a mechanism of impaired M. avium killing in CF. IMPORTANCE Mycobacterium avium is a member of a group of bacterial species termed nontuberculous mycobacteria (NTM) that cause lung disease in certain populations, including persons with cystic fibrosis (CF). NTM infections are challenging to diagnose and can be even more difficult to treat. This study investigated how the immune system responds to M. avium infection in CF. We found that neutrophils, the most abundant immune cell in the lungs in CF, can effectively kill M. avium in individuals both with and without CF. Another component of the immune response called the complement system is also required for this process. Levels of complement proteins are altered in persons with CF who have a history of NTM compared to those without a history of NTM infection. These results add to our understanding of how the immune system responds to M. avium, which can help pave the way toward better diagnostic and treatment strategies.
影响因子：
3.7
作者：
Kotilainen H;Lokki ML;Paakkanen R;Seppänen M;Tukiainen P;Meri S;Poussa T;Eskola J;Valtonen V;Järvinen A
通讯作者：
Järvinen A