Waters W R, Thacker T C, Nonnecke B J, Palmer M V, Schiller I, Oesch B, Vordermeier H M, Silva E, Estes D M
National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa, USA.
Clin Vaccine Immunol. 2012 Mar;19(3):346-51. doi: 10.1128/CVI.05657-11. Epub 2012 Jan 11.
Gamma interferon (IFN-γ)-induced protein 10 (IP-10) has recently shown promise as a diagnostic biomarker of Mycobacterium tuberculosis infection of humans. The aim of the current study was to compare IP-10 and IFN-γ responses upon Mycobacterium bovis infection in cattle by using archived samples from two aerosol inoculation studies. In the first study (10(4) CFU M. bovis by aerosol, n = 7), M. bovis purified protein derivative (PPDb)-specific IP-10 and IFN-γ gene expression was detected as early as 29 days after challenge. PPDb-specific IP-10 and IFN-γ mRNA responses followed a similar pattern of expression over the course of this study and were highly correlated (r = 0.87). In the second study (10(5) CFU M. bovis by aerosol, n = 5), IP-10 and IFN-γ (protein) responses to mycobacterial antigens were compared following challenge. IFN-γ responses to mycobacterial antigens were detected at 29 days after challenge and were sustained during the remainder of the study. IFN-γ responses to mycobacterial antigens exceeded corresponding responses in nonstimulated cultures. IP-10 responses to mycobacterial antigens exceeded preinfection responses at 7, 29, and 63 days after challenge. In contrast to IFN-γ responses, IP-10 responses to mycobacterial antigens generally did not exceed the respective responses in nonstimulated cultures. IP-10 responses to medium alone and to mycobacterial antigens followed a similar pattern of response. Correlations between IP-10 and IFN-γ (protein) responses were modest (r ≈ 0.50 to 0.65). Taken together, these findings do not support the use of IP-10 protein as a biomarker for bovine tuberculosis using the current testing protocol and reagents; however, mRNA-based assays may be considered for further analysis.
γ干扰素（IFN-γ）诱导蛋白10（IP-10）最近显示出有望作为人类结核分枝杆菌感染的诊断生物标志物。本研究的目的是通过使用来自两项气溶胶接种研究的存档样本，比较牛感染牛分枝杆菌后IP-10和IFN-γ的反应。在第一项研究中（通过气溶胶接种10⁴CFU牛分枝杆菌，n = 7），早在攻毒后29天就检测到了牛分枝杆菌纯化蛋白衍生物（PPDb）特异性IP-10和IFN-γ基因表达。在本研究过程中，PPDb特异性IP-10和IFN-γ mRNA反应遵循相似的表达模式，且高度相关（r = 0.87）。在第二项研究中（通过气溶胶接种10⁵CFU牛分枝杆菌，n = 5），比较了攻毒后对分枝杆菌抗原的IP-10和IFN-γ（蛋白）反应。在攻毒后29天检测到对分枝杆菌抗原的IFN-γ反应，并在研究的剩余时间内持续存在。对分枝杆菌抗原的IFN-γ反应超过了未刺激培养物中的相应反应。对分枝杆菌抗原的IP-10反应在攻毒后7天、29天和63天超过了感染前反应。与IFN-γ反应相反，对分枝杆菌抗原的IP-10反应通常未超过未刺激培养物中的相应反应。对单独培养基和分枝杆菌抗原的IP-10反应遵循相似的反应模式。IP-10和IFN-γ（蛋白）反应之间的相关性中等（r≈0.50至0.65）。综上所述，这些发现不支持使用IP-10蛋白作为使用当前检测方案和试剂的牛结核病生物标志物；然而，基于mRNA的检测方法可考虑用于进一步分析。
