The role of endogenous interleukin-12 in resistance to murine cytomegalovirus (MCMV) infection and a novel action for endogenous IL-12 p40
The role of endogenous interleukin-12 in resistance to murine cytomegalovirus (MCMV) infection and a novel action for endogenous IL-12 p40
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DOI：
10.1089/107999099313082
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发表时间：
1999-10-01
影响因子：
2.3
通讯作者：
Nash, AA
中科院分区：
文献类型：
--
作者：
Carr, JA;Rogerson, JA;Nash, AA
生物活性白细胞介素-12（IL-12）包含共价连接至35 kDa亚基（p35）的40 kDa亚基（p40），其响应于一系列感染性刺激而产生。在这里，我证明了IL-12 p30（p40（-/-））或IL-12 p35（p35（-/-））缺陷的小鼠在存活方面对鼠巨细胞病毒（MCMV）感染易感。（Balb/c p35（-/-））和病毒清除（Balb/c p35（-/-）和Balb/c p30-/-），并且这种易感性可能与血清干扰素-γ（IFN-γ）水平的缺乏相关。这些数据支持内源性IL-12在控制MCMV感染中的作用。IL-12 p30亚基的产生超过IL-12 p35，迄今为止，过量的内源性p40的功能被认为是IL-12拮抗作用之一，如用外源性p40进行的体内和体外实验所证明的，我们表明，Balb/c p35（-/-）单独在亚致死性感染的存活率和从脾脏清除病毒方面受到显著损害。这些小鼠产生非常早期的IFN-γ峰（感染后8小时）和异常的肿瘤坏死因子-α（TNF-α）峰（感染后2天）。与Balb/c p40（-/-）相比，MCR IV感染显示Balb/c p35（-/-）表型改变，这表明内源性p30可能具有独立于体内IL-12拮抗作用的活性，并且是IL-12拮抗作用的补充。
Biologically active interleukin-12 (IL-12), comprising a 40 kDa subunit (p40) covalently linked to a 35 kDa subunit (p35), is produced in response to a range of infectious stimuli. Here, me demonstrate that mice deficient in either IL-12 p30 (p40(-/-)) or IL-12 p35 (p35(-/-)) are susceptible to murine cytomegalovirus (MCMV) infection in terms of survival (Balb/c p35(-/-)) and viral clearance (Balb/c p35(-/-) and Balb/c p30-/-), and this susceptibility may be correlated to a deficiency in serum interferon-gamma (IFN-gamma) levels. These data support a role for endogenous IL-12 in controlling MCMV infection. The IL-12 p30 subunit is produced in excess of IL-12 p35, and to date the function of the excess endogenous p40 has been assumed to be one of IL-12 antagonism, as demonstrated by experiments with exogenous p40 both in vivo and in vitro, We show that Balb/c p35(-/-) alone are significantly compromised in survival of a sublethal infection and in clearance of virus from the spleen. These mice produce a very early IFN-gamma spike (8 h after infection) and an aberrant tumor necrosis factor-alpha (TNF-alpha) spike (day 2 after infection). MCR IV infection has revealed an altered Balb/c p35(-/-) phenotype compared with Balb/c p40(-/-), and this indicates that endogenous p30 may have an activity independent of and additional to IL-12 antagonism in vivo.