Author:
Bist Pradeep,Dikshit Neha,Koh Tse Hsien,Mortellaro Alessandra,Tan Thuan Tong,Sukumaran Bindu
Abstract
ABSTRACTAcinetobacter baumanniiis a major extensively drug-resistant lethal human nosocomial bacterium. However, the host innate immune mechanisms controllingA. baumanniiare not well understood. Although viewed as an extracellular pathogen,A. baumanniican also invade and survive intracellularly. However, whether host innate immune pathways sensing intracellular bacteria contribute to immunity againstA. baumanniiis not known. Here, we provide evidence for the first time that intracellular antibacterial innate immune receptors Nod1 and Nod2, and their adaptor Rip2, play critical roles in the sensing and clearance ofA. baumanniiby human airway epithelial cellsin vitro.A. baumanniiinfection upregulated Rip2 expression. Silencing of Nod1, Nod2, and Rip2 expression profoundly increased intracellular invasion and prolonged the multiplication and survival ofA. baumanniiin lung epithelial cells. Notably, the Nod1/2-Rip2 axis did not contribute to the control ofA. baumanniiinfection of human macrophages, indicating that they play cell type-specific roles. The Nod1/2-Rip2 axis was needed forA. baumanniiinfection-induced activation of NF-κB but not mitogen-activated protein kinases. Moreover, the Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses toA. baumanniiinfection. Mechanistic studies showed that the Nod1/2 pathway contributed to the innate control ofA. baumanniiinfection through the production of β-defensin 2 by airway epithelial cells. This study revealed new insights into the immune control ofA. baumanniiand may contribute to the development of effective immune therapeutics and vaccines againstA. baumannii.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
49 articles.
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