PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
包封的细菌如a型流感嗜血杆菌(Hia)的有效消除依赖于免疫机制,例如通过中性粒细胞的补体介导的调理吞噬作用与通过抗胶囊抗体的调理作用相协调。该研究评估了Hia是否可以通过嗜中性粒细胞激活免疫应答,以及这些应答在包封的菌株与未包封的菌株或侵袭性菌株与非侵袭性菌株之间是否不同。
■HL-60来源的中性粒细胞样细胞（dHL-60），用1.25%二甲基亚砜在9天内分化，在调理吞噬试验和体外感染模型中使用Hia对杀伤和dHL-60表面分子表达的敏感性，分别。使用北美优势序列型（ST）-23的临床分离株，包括Hia11-139（封装，侵入性)，14-61（封装，非侵入性)，13-0074(未封装,侵入性)，以及代表性的ST-4分离株(Hia13-240，封装，侵入性)，和一种不可分型的菌株(NTHi375，未封装，非侵入性)。
■未封装和非侵入性Hi菌株更容易被先天免疫反应杀死，而ST-23侵入性菌株，Hia11-139需要血清抗体进行破坏。流式细胞术分析显示共刺激分子ICAM-1和Fc受体（CD89，CD64）的表达增加，但Fc受体CD16的表达降低，揭示了嗜中性粒细胞介导的针对Hia的防御的潜在机制，扩展到非侵入性和侵入性菌株。
■具有不同致病性的Hia临床分离株表明，在保持相同的激活中性粒细胞样细胞能力的同时，对免疫机制杀伤的敏感性形成对比。进一步强调需要进一步研究Hia的发病机制。
■HL-60来源的中性粒细胞样细胞（dHL-60），用1.25%二甲基亚砜在9天内分化，在调理吞噬试验和体外感染模型中使用Hia对杀伤和dHL-60表面分子表达的敏感性，分别。使用北美优势序列型（ST）-23的临床分离株，包括Hia11-139（封装，侵入性)，14-61（封装，非侵入性)，13-0074(未封装,侵入性)，以及代表性的ST-4分离株(Hia13-240，封装，侵入性)，和一种不可分型的菌株(NTHi375，未封装，非侵入性)。
■未封装和非侵入性Hi菌株更容易被先天免疫反应杀死，而ST-23侵入性菌株，Hia11-139需要血清抗体进行破坏。流式细胞术分析显示共刺激分子ICAM-1和Fc受体（CD89，CD64）的表达增加，但Fc受体CD16的表达降低，揭示了嗜中性粒细胞介导的针对Hia的防御的潜在机制，扩展到非侵入性和侵入性菌株。
■具有不同致病性的Hia临床分离株表明，在保持相同的激活中性粒细胞样细胞能力的同时，对免疫机制杀伤的敏感性形成对比。进一步强调需要进一步研究Hia的发病机制。
