The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection
The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection
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DOI：
10.1371/journal.ppat.1008464
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发表时间：
2020-04-01
期刊：
影响因子：
6.7
通讯作者：
Andrew, Peter W.
中科院分区：
文献类型：
--
作者：
Fernandes, Vitor E.;Ercoli, Giuseppe;Andrew, Peter W.
肺炎链球菌是一种主要的人类病原体，可引起肺炎和败血症。遗传成分强烈影响宿主对肺炎球菌感染的反应，但负责的位点尚不清楚。我们之前已经从易感小鼠菌株CBA/Ca中发现了小鼠7号染色体上的一个位点，该位点对肺炎球菌感染至关重要。在这里，我们确定了一个负责基因Cd22，它在CBA/Ca菌株中携带一个点突变，导致B细胞上Cd22的丢失。CBA/Ca小鼠和C57BL/6背景的基因靶向cd22缺陷小鼠对肺炎球菌感染的易感性相似，如肺部细菌复制、高菌血症和早期死亡所示。细菌感染后，cd22缺陷小鼠肺部的B细胞数量大幅减少，包括产生GM-CSF、分泌IgM的先天反应激活剂B细胞，这对保护至关重要。这项研究提供了令人震惊的证据，证明CD22对侵袭性肺炎球菌疾病的保护至关重要。作者总结肺炎链球菌（又称肺炎球菌）是一种人类细菌病原体，可导致肺炎和败血症等疾病，导致数百万人患病和死亡。对肺炎球菌感染的易感性与遗传成分有关，这些遗传成分强烈影响感染者对感染的反应，但对致病基因和控制感染的机制知之甚少。在以前的研究中，我们发现小鼠菌株之间对肺炎球菌感染的易感性和耐药性存在很大差异。在这项研究中，我们发现了一种基因，Cd22基因，它控制着对肺炎球菌感染的抵抗力。没有b细胞特异性CD22蛋白的小鼠更容易感染肺炎链球菌。我们可以证明，在cd22缺陷小鼠中，在肺炎球菌感染期间迁移到肺部的保护性B细胞群缺失。该研究显示了CD22的新作用，并指出了治疗肺炎球菌感染的新潜在靶点。
Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.Author summaryStreptococcus pneumoniae (known as the pneumococcus) is a human bacterial pathogen responsible for diseases such as pneumonia and sepsis, that cause illness and death in millions of individuals. Susceptibility to pneumococcal infections is associated with genetic components that strongly influence how infected individuals respond to infection, but little is known about the causal gene(s) and the mechanisms of control of the infection. In previous studies we have found strong differences in susceptibility and resistance to pneumococcal infections between mouse strains. In this study we identified a gene, the Cd22 gene, that controls resistance to pneumococcal infection. Mice without the B-cell specific CD22 protein were much more susceptible to infection with S. pneumoniae. We could show that a protective population of B cells that migrates to the lung during pneumococcal infection is missing in Cd22-deficient mice. The study shows to a new role for CD22 and indicates a new potential target for treatment of pneumococcal infections.