Neutrophil production of IL-12 and other cytokines during microbial infection.
Neutrophil production of IL-12 and other cytokines during microbial infection.
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DOI：
10.1159/000071557
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
E. Denkers;L. Del Río;Soumaya Bennouna
中科院分区：
文献类型：
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作者：
E. Denkers;L. Del Río;Soumaya Bennouna
The concept that neutrophils are an important source of cytokines such as IL-12 is a relatively new idea that is gaining increasing acceptance as more studies are reported. Polymorphonuclear leukocytes (PMN) are exquisitely tuned to respond to microbial challenge, and it is well-known that these cells accumulate rapidly (often within minutes or hours) and in large numbers at sites of infection. Neutrophils generally produce lower amounts of cytokine on a per cell basis than do macrophages or dendritic cells (DC)[1]. Nevertheless, PMN are by far the most common leukocyte type. The fact that they often vastly outnumber other cells at sites of infection argues very strongly that neutrophils are a physiologically important source of cytokines that play a critical role in determining the outcome of infectious disease. A number of recent studies, described in this chapter, provide compelling evidence that this is the case, particularly with regard to IL-12.The cytokine IL-12 itself is a 70-kD heterodimer composed of constitutive 35-kD and inducible 40-kD subunits and is produced by macrophages, DC and neutrophils [2]. The primary function of IL-12 is to promote IFN-y responses by driving differentiation of naïve T lymphocytes into Th1 cells, as well as by promoting NK cell production of this cytokine. IL-12 also plays an important role in CD8 T lymphocyte differentiation into cytolytic T cell effectors that can also be an important IFN-y source [2]. Whether IL-12 functions in Th1 differentiation to instruct cell fate through chromatin remodeling, or whether the cytokine selects T lymphocytes whose fate has been prespecified by master regulatory molecules such as T-bet is an area of current debate [3, 4]. Whatever the case, IL-12 is regarded as the central cytokine which bridges innate and acquired
