Boucherit Nicolas, Barry Abdoulaye Oury, Mottola Giovanna, Trouplin Virginie, Capo Christian, Mege Jean-Louis, Ghigo Eric
URMITE, CNRS UMR 6236-IRD 198, Université de la Méditerranée, Marseille, France.
FEMS Immunol Med Microbiol. 2012 Feb;64(1):101-3. doi: 10.1111/j.1574-695X.2011.00852.x. Epub 2011 Aug 30.
Q fever is a disease caused by Coxiella burnetii, an obligate intracellular bacterium. Acute Q fever is characterized by efficient immune response, whereas chronic Q fever is characterized by dysregulated immune response as demonstrated by the lack of granulomas, the failure of C. burnetii to induce lymphoproliferation, and interferon-γ production. The mitogen-activated protein kinase (MAPK) signaling pathway plays crucial roles in innate immune responses and control of bacterial infections. However, its role in Q fever has not been addressed. First, we investigated the activation of MAPKs p38, c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) 1/2 in murine macrophages stimulated with C. burnetii. Coxiella burnetii NM phase I (virulent) and NM phase II (avirulent) induced the activation of JNK and ERK1/2. Avirulent C. burnetii activate p38, whereas C. burnetii did not induce the phosphorylation of p38. Second, the level of p38 activation was studied in Q fever patients. We found that p38 was activated in monocyte-derived macrophages from healthy donors and patients with acute Q fever in response to a potent agonist such as lipopolysaccharide. Interestingly, p38 was not activated in patients with active chronic Q fever and was activated in patients with cured chronic Q fever. These results suggest that the determination of p38 activation may serve as a tool for measuring Q fever activity.
Q热是一种由专性细胞内细菌伯氏考克斯体引起的疾病。急性Q热的特征是有效的免疫反应，而慢性Q热的特征是免疫反应失调，表现为缺乏肉芽肿、伯氏考克斯体无法诱导淋巴细胞增殖以及干扰素-γ产生。丝裂原活化蛋白激酶（MAPK）信号通路在先天性免疫反应和细菌感染控制中起关键作用。然而，其在Q热中的作用尚未得到探讨。首先，我们研究了用伯氏考克斯体刺激的小鼠巨噬细胞中MAPKs p38、c-jun N末端激酶（JNK）和细胞外信号调节激酶（ERK）1/2的激活情况。伯氏考克斯体NM I期（有毒力）和NM II期（无毒力）诱导了JNK和ERK1/2的激活。无毒力的伯氏考克斯体激活p38，而伯氏考克斯体未诱导p38的磷酸化。其次，我们研究了Q热患者中p38的激活水平。我们发现，来自健康供体和急性Q热患者的单核细胞衍生巨噬细胞在响应脂多糖等强效激动剂时p38被激活。有趣的是，活动性慢性Q热患者的p38未被激活，而治愈的慢性Q热患者的p38被激活。这些结果表明，p38激活的测定可能作为衡量Q热活动的一种工具。
