Palaniappan Ravichandran, Singh Shailesh, Singh Udai P, Singh Rajesh, Ades Edwin W, Briles David E, Hollingshead Susan K, Royal Walter, Sampson Jacquelyn S, Stiles Jonathan K, Taub Dennis D, Lillard James W
Mercer University, Atlanta, GA 30341, USA.
J Immunol. 2006 Feb 15;176(4):2346-56. doi: 10.4049/jimmunol.176.4.2346.
Understanding the requirements for protection against pneumococcal carriage and pneumonia will greatly benefit efforts in controlling these diseases. Recently, it has been shown that genetic polymorphisms can result in diminished expression of CCL5, which results in increased susceptibility to and progression of infectious diseases. We show that CCL5, together with Th cytokine mRNA expression, is temporally up-regulated during pneumococcal carriage. To determine the contribution of CCL5 to pneumococcal surface antigen A-specific humoral and cellular pneumococcal immunity, mice were treated with anti-CCL5 or control Abs before and during Streptococcus pneumoniae strain EF3030-challenge for the initiation of carriage. CCL5 blockade resulted in a decrease of CD4(+) and CD8(+) T cells as well as CD11b(+) cells in the spleen, cervical lymph node, lung, and nasopharyngeal associated lymphoid tissue during the recognition phase of the pneumococcal adaptive immune response. CCL5 blockade significantly reduced the Ag-specific IgG2a and IgG1 Abs in serum and IgA Ab levels in nasal washes. These decreases also corresponded to reductions in Ag-specific T cell (mucosal and systemic) responses. CCL5 inhibition resulted in decreasing the quantity of IL-4- and IFN-gamma-secreting CD4(+) T cells and increasing the number of Ag-specific IL-10-producing CD4(+) T cells; these changes combined also corresponded with the transition from pneumococcal carriage to lethal pneumonia. These data suggest that CCL5 is an essential factor for the induction and maintenance of protective pneumococcal immunity.
了解预防肺炎球菌携带和肺炎的要求将极大地有助于控制这些疾病的工作。最近的研究表明，基因多态性可导致CCL5表达减少，从而增加对传染病的易感性和疾病进展。我们发现，在肺炎球菌携带期间，CCL5与Th细胞因子mRNA表达一起会出现暂时性上调。为了确定CCL5对肺炎球菌表面抗原A特异性体液免疫和细胞免疫的贡献，在肺炎链球菌EF3030株攻击引发携带的过程中，对小鼠在攻击前后用抗CCL5或对照抗体进行处理。在肺炎球菌适应性免疫反应的识别阶段，阻断CCL5导致脾脏、颈部淋巴结、肺和鼻咽相关淋巴组织中的CD4(+)和CD8(+) T细胞以及CD11b(+)细胞数量减少。阻断CCL5可显著降低血清中抗原特异性IgG2a和IgG1抗体以及鼻腔灌洗液中IgA抗体水平。这些降低也与抗原特异性T细胞（黏膜和全身）反应的减少相对应。抑制CCL5导致分泌IL-4和IFN-γ的CD4(+) T细胞数量减少，而产生抗原特异性IL-10的CD4(+) T细胞数量增加；这些变化共同也与从肺炎球菌携带向致死性肺炎的转变相对应。这些数据表明，CCL5是诱导和维持保护性肺炎球菌免疫的关键因素。
