期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 84, 期 4, 页码 1141-1150出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0208118
关键词
bacterial meninigits; complement receptor 3
资金
- NIAID NIH HHS [R01 AI065495, AI65495, AI68150, R01 AI068150] Funding Source: Medline
Myeloid cells, including neutrophils and macrophages, play important roles in innate immune defense against acute bacterial infections. Myeloid Src family kinases (SFKs) p59/61(hck) (Hck), p58(c-fgr) (Fgr), and p53/56(lyn) (Lyn) are known to control integrin beta(2) signal transduction and Fc gamma R-mediated phagocytosis in leukocytes. In this study, we show that leukocyte recruitment into the cerebrospinal fluid space and bacterial clearance is hampered in mice deficient in all three myeloid SFKs (hck(-/-) fgr(-/-) lyn(-/-)) during pneumococcal meningitis. As a result, the hck(-/-) fgr(-/-) lyn(-/-) mice developed increased intracranial pressure and a worse clinical outcome ( increased neurologic deficits and mortality) compared with wildtype mice. Impaired bacterial killing was associated with a lack of phagocytosis and superoxide production in triple knockout neutrophils. Moreover, in hck(-/-) fgr(-/-) lyn(-/-) neutrophils, phosphorylation of p40(phox) was absent in response to pneumococcal stimulation, indicating a defect in NAPDH oxidase activation. Mice lacking the complement receptor 3 (CR3; CD11b/CD18), which belongs to the beta(2)- integrin family, also displayed impaired host defense against pneumococci, along with defective neutrophil superoxide production, but cerebrospinal fluid pleocytosis was normal. Cerebral expression of cytokines and chemokines was not decreased in both mouse strains, indicating that CR3 and myeloid SFKs are dispensable for the production of inflammatory mediators. Thus, our study demonstrates the pivotal role of myeloid SFKs and CR3 in mounting an effective defense against CNS infection with Streptococcus pneumonia by regulating phagocytosis and NADPH oxidase-dependent superoxide production. These data support the role of SFKs as critical mediators of CR3 signal transduction in host defense.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据