Nod1, Nod2 and Rip2 axis contributes to host immune defense against intracellular Acinetobacter baumannii infection

Nod1, Nod2 and Rip2 axis contributes to host immune defense against intracellular Acinetobacter baumannii infection
Title:
Nod1, Nod2 and Rip2 axis contributes to host immune defense against intracellular Acinetobacter baumannii infection
Other Titles:
Infection and Immunity
Keywords:
Publication Date:
23 December 2013
Citation:
Abstract:
Acinetobacter baumannii is a major extensively drug-resistant lethal human nosocomial-bacterium. Yet, the host innate-immune mechanisms controlling A. baumannii are less understood. Although viewed as an extracellular-pathogen, A. baumannii can also invade and survive intracellularly. However, whether host innate-immune pathways sensing intracellular-bacteria contribute to immunity against A. baumannii is not known. Here, we provide evidence for the first time that intracellular anti-bacterial innate-immune receptors Nod1 and Nod2, and their adaptor Rip2, play critical roles in sensing and clearance of A. baumannii by human airway epithelial cells in vitro. A. baumannii infection up-regulated Rip2 expression. Silencing of Nod1, Nod2 and Rip2 expression profoundly increased intracellular invasion, and prolonged the multiplication and survival of A. baumannii in lung epithelial cells. Notably, the Nod1/2-Rip2 axis did not contribute to the control of A. baumannii infection of human macrophages, indicating that they play cell type specific roles. Nod1/2-Rip2 axis was needed for A.baumannii infection-induced activation of NF-κB, but not MAP kinases. Moreover, Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine response to A. baumannii infection. Mechanistic studies showed that Nod1/2 pathway contributed to the innate control of A. baumannii infection through the production of β-defensin 2 by airway epithelial cells. This study revealed new insights into the immune control of A. baumannii, and may contribute to the development of effective immune therapeutics and vaccines against A. baumannii.
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PublisherCopyrights
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ISSN:
0019-9567
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