Mycobacterium avium Biofilm Attenuates Mononuclear Phagocyte Function by Triggering Hyperstimulation and Apoptosis during Early Infection
Mycobacterium avium Biofilm Attenuates Mononuclear Phagocyte Function by Triggering Hyperstimulation and Apoptosis during Early Infection
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DOI：
10.1128/iai.00820-13
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发表时间：
2014-01-01
影响因子：
3.1
通讯作者：
Bermudez, Luiz E.
中科院分区：
文献类型：
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作者：
Rose, Sasha J.;Bermudez, Luiz E.
鸟分枝杆菌亚种。人感染是一种机会致病菌，已被证明在体外和体内都能形成生物膜。体内生物膜的形成似乎与宿主呼吸道的感染有关。禽类分支杆菌亚种是如何形成的。人的生物膜被允许在没有被先天免疫系统清除的情况下建立并持续存在，目前尚不清楚。为了确定这一机制，我们利用THP-1人单核巨噬细胞与已建立的M.avium亚种共培养建立了体外模型。研究了相互作用的各个方面，包括吞噬细胞的刺激和反应、细菌杀灭和细胞凋亡。鸟霉亚种。人血清白蛋白生物膜可刺激THP-1细胞释放肿瘤坏死因子α(TNF-α)，并产生超氧化物和一氧化氮。令人惊讶的是，过度刺激的吞噬细胞并没有有效地清除生物膜的细胞，即使在预先刺激了干扰素(干扰素)或肿瘤坏死因子-α或与自然杀伤细胞(已被证明可以诱导抗M。禽类亚种当加入到感染了浮游鸟分支杆菌亚种的THP-1细胞中时，人的感染活性。人)。时间推移显微镜和TUNEL(末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记)试验确定了与禽类分支杆菌亚种的接触。人的生物被膜导致了早期的、广泛的细胞凋亡，直到很晚才在浮游的鸟分枝杆菌亚种中发现。人感染。在与生物膜相互作用过程中阻断肿瘤坏死因子-α或肿瘤坏死因子-R1可显著减少THP-1的凋亡，但并不能消除鸟分枝杆菌亚种。原始人。我们的数据总体上表明，鸟分枝杆菌亚种。人血生物膜可诱导肿瘤坏死因子-α诱导的巨噬细胞过度刺激和细胞凋亡，从而阻止天然免疫系统细胞清除生物膜，使生物膜相关感染得以持续。
Mycobacterium avium subsp. hominissuis is an opportunistic human pathogen that has been shown to form biofilm in vitro and in vivo. Biofilm formation in vivo appears to be associated with infections in the respiratory tract of the host. The reasoning behind how M. avium subsp. hominissuis biofilm is allowed to establish and persist without being cleared by the innate immune system is currently unknown. To identify the mechanism responsible for this, we developed an in vitro model using THP-1 human mononuclear phagocytes cocultured with established M. avium subsp. hominissuis biofilm and surveyed various aspects of the interaction, including phagocyte stimulation and response, bacterial killing, and apoptosis. M. avium subsp. hominissuis biofilm triggered robust tumor necrosis factor alpha (TNF-alpha) release from THP-1 cells as well as superoxide and nitric oxide production. Surprisingly, the hyperstimulated phagocytes did not effectively eliminate the cells of the biofilm, even when prestimulated with gamma interferon (IFN-gamma) or TNF-alpha or cocultured with natural killer cells (which have been shown to induce anti-M. avium subsp. hominissuis activity when added to THP-1 cells infected with planktonic M. avium subsp. hominissuis). Time-lapse microscopy and the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay determined that contact with the M. avium subsp. hominissuis biofilm led to early, widespread onset of apoptosis, which is not seen until much later in planktonic M. avium subsp. hominissuis infection. Blocking TNF-alpha or TNF-R1 during interaction with the biofilm significantly reduced THP-1 apoptosis but did not lead to elimination of M. avium subsp. hominissuis. Our data collectively indicate that M. avium subsp. hominissuis biofilm induces TNF-alpha-driven hyperstimulation and apoptosis of surveilling phagocytes, which prevents clearance of the biofilm by cells of the innate immune system and allows the biofilm-associated infection to persist.