Induction of interleukin-12 and gamma interferon requires tumor necrosis factor alpha for protective T1-cell-mediated immunity to pulmonary Cryptococcus neoformans infection
Induction of interleukin-12 and gamma interferon requires tumor necrosis factor alpha for protective T1-cell-mediated immunity to pulmonary Cryptococcus neoformans infection
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DOI：
10.1128/iai.70.6.2959-2964.2002
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发表时间：
2002-06-01
影响因子：
3.1
通讯作者：
Huffnagle, GB
中科院分区：
文献类型：
--
作者：
Herring, AC;Lee, J;Huffnagle, GB
T1细胞介导的免疫的发展是需要清除肺部新生隐球菌感染。这些研究的目的是确定肿瘤坏死因子α（TNF-α）增强肺T1免疫对C的发展的机制。新生儿感染。在C.新生儿感染。在反应传入阶段（第0 - 7天）检查的任何时间点，对照组和抗TNF-α给药组小鼠的肺中CFU数量均无差异。然而，TNF-α的中和阻止了在反应的传出相（第14天）期间肺清除的启动。给予抗TNF-α单克隆抗体（第0天）降低了由C.感染后第7天的新生儿。TNF-α的中和作用（第0天）也改变了C.新生儿感染。抗TNF-α治疗的小鼠在感染后第14天出现肺嗜酸性粒细胞增多症。与肺嗜酸性粒细胞增多症一致，抗TNF-α处理的小鼠表现出血清免疫球蛋白E升高和抗隐球菌迟发型超敏反应抑制，表明向T2反应转变。IL-12的中和也阻止了肺白细胞响应感染产生IFN-γ。这些发现表明，传入相TNF-α的产生对于诱导IL-12和IFN-γ是必不可少的，中和或早期TNF-α导致抗真菌免疫的T1/T2平衡的T2偏移。
The development of T1-cell-mediated immunity is required to clear a pulmonary Cryptococcus neoformans infection. The objective of these studies was to determine the mechanism by which tumor necrosis factor alpha (TNF-alpha) augments the development of pulmonary T1 immunity to C. neoformans infection. TNF-alpha expression was detected in lavage sample cells at days 2, 3, and 7 following C. neoformans infection. The numbers of CFU in the lung were not different between control and anti-TNF-alpha-treated mice at any time point examined during the afferent phase of the response (days 0 to 7). However, neutralization of TNF-alpha prevented the initiation of pulmonary clearance during the efferent phase of the response (day 14). Administration of anti-TNF-alpha monoclonal antibody (day 0) diminished the lung levels of TNF-alpha, interleukin-12 (IL-12), and gamma interferon (IFN-gamma) induced by C. neoformans at day 7 postinfection. Neutralization of TNF-alpha (day 0) also altered the IFN-gamma/IL-4 ratio in the lung-associated lymph nodes at day 7 following C. neoformans infection. Anti-TNF-alpha-treated mice developed a pulmonary eosinophilia at day 14 postinfection. Consistent with the pulmonary eosinophilia, anti-TNF-alpha-treated mice exhibited elevated serum immunoglobulin E and inhibition of the anticryptococcal delayed-type hypersensitivity response, indicating a shift toward a T2 response. Neutralization of IL-12 also prevented lung leukocyte production of IFN-gamma in response to the infection. These findings demonstrate that afferent-phase TNF-alpha production is essential for the induction of IL-12 and IFN-gamma and neutralization or early TNF-alpha results in a T2 shift of the T1/T2 balance of antifungal immunity.