科研之友
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摘要
Tularemia is a vector-borne zoonosis caused by Ft, a Gram-negative, facultative intracellular bacterium. Ft exists in two clinically relevant forms, the European biovar B (holarctica), which produces acute, although mild, self-limiting infections, and the more virulent United States biovar A (tularensis), which is often associated with pneumonic tularemia and more severe disease. In a mouse model of tularemia, respiratory infection with the virulence-attenuated Type B (LVS) or highly virulent Type A (SchuS4) strain engenders peribronchiolar and perivascular inflammation. Paradoxically, despite an intense neutrophilic infiltrate and high bacterial burden, T(H)1-type proinflammatory cytokines (e. g., TNF, IL-1 beta, IL-6, and IL-12) are absent within the first similar to 72 h of pulmonary infection. It has been suggested that the bacterium has the capacity to actively suppress or block NF-kappa B signaling, thus causing an initial delay in up-regulation of inflammatory mediators. However, our previously published findings and those presented herein contradict this paradigm and instead, strongly support an alternative hypothesis. Rather than blocking NF-kappa B, Ft actually triggers TLR2-dependent NF-kappa B signaling, resulting in the development and activation of tDCs and the release of anti-inflammatory cytokines (e. g., IL-10 and TGF-beta). In turn, these cytokines stimulate development and proliferation of T-regs that may restrain T(H)1-type proinflammatory cytokine release early during tularemic infection. The highly regulated and overall anti-inflammatory milieu established in the lung is permissive for unfettered growth and survival of Ft. The capacity of Ft to evoke such a response represents an important immune-evasive strategy. J. Leukoc. Biol. 90: 493-507; 2011.
- 出版日期2011-9
