Nocodazole treatment interrupted Brucella abortus invasion in RAW 264.7 cells, and successfully attenuated splenic proliferation with enhanced inflammatory response in mice

Issue Date

2-2017

Abstract

Brucellosis is one of the most important and widespread zoonosis worldwide responsible for serious economic losses and considerable public health burden. In this study, we investigated the modulatory effect of a microtubule-inhibitor, nocodazole, on B. abortus infection in murine macrophages and in a mouse model. Nocodazole activated macrophages and directly inhibited the growth of Brucella in a dose-dependent manner. Nocodazole increased adhesion but reduced invasion and intracellular growth of Brucella in macrophages although it did not affect co-localization of Brucella with LAMP-1. In addition, nocodazole negatively affected actin polymerization, and weakly activated ERK and p38α but significantly activated JNK in non-infected cells. After subsequent infection, nocodazole weakly inhibited activation of ERK and p38α. For the in vivo tests, nocodazole -treated mice displayed elevated levels of IFN-γ, MCP-1 and IL-10 while Brucella-infected nocodazole -treated mice showed high levels of TNF, IFN-γ, MCP-1, IL-10 and IL-6 as compared to controls. Furthermore, nocodazole treatment reduced inflammation and Brucella proliferation in the spleens of mice. These findings highlight the potential use of nocodazole for the control of brucellosis although further investigations are encouraged to validate its therapeutic use in animal hosts.

Source or Periodical Title

Microbial Pathogenesis

ISSN

0882-4010

Volume

103

Page

87-93

Document Type

Article

Language

English

Subject

B. abortus, Cytokine, F-actin, Macrophages, MAPKs, Nocodazole

Identifier

doi: 10.1016/j.micpath.2016.11.028.

Digital Copy

yes

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