Xu Da, Gu Yujie, Li Guilian, Wang Ruihuan, Xiao Shiqi, Duan Hongyang, Jiang Jingwei, Zhao Xiuqin, Wan Kanglin, He Xinyue, Liu Haican, Lou Yongliang
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
BMC Microbiol. 2025 Jan 9;25(1):9. doi: 10.1186/s12866-024-03724-4.
Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium abscessus (M. abscessus) are important pathogens that can cause lung diseases. Given the abundance of shared antigens between these two pathogens, evaluating the cross-immunization between Mycobacterium tuberculosis and Mycobacterium abscessus has implications for the assessment of tuberculosis vaccines based on nontuberculous mycobacteria (NTM). The whole-cell proteins of Mycobacterium abscessus were lysed via ultrasonication and then were subcutaneously injected into BALB/c mice either alone or mixed with adjuvant for three times at a 10-day interval. After the final immunization, cross-immune antigens were analysed via genomic comparison and Mycobacterium tuberculosis proteome microarrays. BALB/c mice splenic lymphocytes were stimulated with TB-PPD to assess the cross-immunity of the cellular immune response. The effect of cross-immunity on the growth of Mycobacterium tuberculosis was evaluated using a Mycobacterium tuberculosis growth inhibition assay. Despite the presence of 1,953 homologous gene clusters between Mycobacterium tuberculosis and Mycobacterium abscessus, only 302 Mycobacterium tuberculosis antigens exhibited cross-immunoreactivity after three immunizations. Compared with the PBS group, TB-PPD stimulation significantly increased the secretion of TNF-α, IL-4, and IL-6 by sensitized mouse splenic lymphocytes, and significantly affected the proliferation of IL-2CD4 T and TNF-αCD4 T cells in the immunized group (P < 0.05), but had no impact on IFN-γ and IFN-γ CD4 T cells. Furthermore, there was no significant difference in the proliferation of Mycobacterium tuberculosis between the immunized group and the PBS group in spleen cells. These data indicate that proteins from Mycobacterium abscessus are highly immunogenic in mice. However, the cross-immune response between Mycobacterium abscessus and Mycobacterium tuberculosis was inadequate to effectively inhibit the proliferation of Mycobacterium tuberculosis.
结核分枝杆菌（M. tuberculosis）和脓肿分枝杆菌（M. abscessus）是可导致肺部疾病的重要病原体。鉴于这两种病原体之间存在大量共享抗原，评估结核分枝杆菌和脓肿分枝杆菌之间的交叉免疫对于基于非结核分枝杆菌（NTM）的结核病疫苗评估具有重要意义。通过超声处理裂解脓肿分枝杆菌的全细胞蛋白，然后将其单独或与佐剂混合，以10天的间隔皮下注射到BALB/c小鼠体内三次。末次免疫后，通过基因组比较和结核分枝杆菌蛋白质组芯片分析交叉免疫抗原。用结核菌素纯蛋白衍生物（TB-PPD）刺激BALB/c小鼠脾淋巴细胞，以评估细胞免疫反应的交叉免疫。使用结核分枝杆菌生长抑制试验评估交叉免疫对结核分枝杆菌生长的影响。尽管结核分枝杆菌和脓肿分枝杆菌之间存在1953个同源基因簇，但三次免疫后只有302种结核分枝杆菌抗原表现出交叉免疫反应性。与磷酸盐缓冲液（PBS）组相比，TB-PPD刺激显著增加了致敏小鼠脾淋巴细胞分泌肿瘤坏死因子-α（TNF-α）、白细胞介素-4（IL-4）和白细胞介素-6（IL-6），并显著影响免疫组中白细胞介素-2 CD4 T细胞和TNF-α CD4 T细胞的增殖（P < 0.05），但对干扰素-γ（IFN-γ）和IFN-γ CD4 T细胞没有影响。此外，免疫组和PBS组脾细胞中结核分枝杆菌的增殖没有显著差异。这些数据表明，脓肿分枝杆菌的蛋白质在小鼠中具有高度免疫原性。然而，脓肿分枝杆菌和结核分枝杆菌之间的交叉免疫反应不足以有效抑制结核分枝杆菌增殖。
