侵袭性和非侵袭性临床 A 型流感嗜血杆菌分离物激活体外分化的 HL-60 细胞

Q1 Medicine Pathogens and Immunity Pub Date : 2024-04-17 DOI:10.20411/pai.v9i1.659
Courtney Ferris, Marina Ulanova
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引用次数: 0

摘要

背景:有效清除像甲型流感嗜血杆菌(Hia)这样的包裹细菌依赖于免疫机制,如中性粒细胞介导的补体吞噬作用与抗包裹抗体的疏松作用。本研究评估了 Hia 是否能通过中性粒细胞激活免疫反应,以及这些反应在有包膜与无包膜或侵袭性与非侵袭性菌株之间是否存在差异。方法:在 1.25% 二甲基亚砜中分化 9 天的 HL-60 衍生中性粒细胞样细胞(dHL-60)被用于溶蛋白吞噬试验和体外感染模型,以分别测量 Hia 的杀灭敏感性和 dHL-60 表面分子的表达。利用北美主要序列类型(ST)-23的临床分离株,包括Hia 11-139(包囊型,侵袭性)、14-61(包囊型,非侵袭性)、13-0074(无包囊型,侵袭性),以及具有代表性的ST-4分离株(Hia 13-240,包囊型,侵袭性)和非类型化菌株(NTHi 375,无包囊型,非侵袭性),研究了菌株特异性特征对免疫反应的影响:结果:无包囊和非侵袭性 Hi 菌株更容易被先天性免疫反应杀死,而 ST-23 侵袭性菌株 Hia 11-139 则需要血清抗体才能消灭。流式细胞术分析表明,共刺激分子ICAM-1和Fc受体(CD89、CD64)的表达量增加,但Fc受体CD16的表达量减少,这揭示了中性粒细胞介导的针对Hia的潜在防御机制,这种机制同时适用于非侵袭性和侵袭性菌株:结论:具有不同致病性的Hia临床分离株显示了对免疫机制杀灭的不同敏感性,同时保持了激活中性粒细胞样细胞的相同能力,这进一步强调了对Hia发病机制进行更多研究的必要性。
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Invasive and Non-invasive Clinical Haemophilus influenzae Type A Isolates Activate Differentiated HL-60 Cells In Vitro
Background: The effective elimination of encapsulated bacteria like Haemophilus influenzae type a (Hia) relies on immune mechanisms such as complement-mediated opsonophagocytosis by neutrophils in coordination with opsonization by anti-capsular antibodies. This study evaluated if Hia could activate the immune response through neutrophils and if these responses differed between encapsulated versus unencapsulated or invasive versus non-invasive strains. Methods: HL-60-derived neutrophil-like cells (dHL-60), differentiated with 1.25% dimethyl sulfoxide over 9 days, were used in an opsonophagocytosis assay and in vitro infection model to measure Hia’s susceptibility to killing and dHL-60 surface molecule expression, respectively. The impact of strain-specific features on the immune response was investigated using clinical isolates of a dominant North American sequence type (ST)-23, including Hia 11-139 (encapsulated, invasive), 14-61 (encapsulated, non-invasive), 13-0074 (unencapsulated, invasive), as well as a representative ST-4 isolate (Hia 13-240, encapsulated, invasive), and a nontypeable strain (NTHi 375, unencapsulated, non-invasive). Results: Unencapsulated and non-invasive Hi strains were more susceptible to killing by the innate immune response while the ST-23 invasive strain, Hia 11-139 required serum antibodies for destruction. Flow cytometry analysis showed increased expression of co-stimulatory molecule ICAM-1 and Fc receptors (CD89, CD64) but decreased expression of the Fc receptor CD16, revealing potential mechanisms of neutrophil-mediated defense against Hia that extend to both non-invasive and invasive strains. Conclusions: Hia clinical isolates with diverse pathogenicity illustrated contrasting susceptibility to killing by immune mechanisms while maintaining the same capacity to activate neutrophil-like cells, further underscoring the need for additional studies on Hia’s pathogenesis.
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来源期刊
Pathogens and Immunity
Pathogens and Immunity Medicine-Infectious Diseases
CiteScore
10.60
自引率
0.00%
发文量
16
审稿时长
10 weeks
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