The Macrophage-Specific Promoter mfap4 Allows Live, Long-Term Analysis of Macrophage Behavior during Mycobacterial Infection in Zebrafish.

Loading...
Thumbnail Image

Date

2015

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

204
views
238
downloads

Citation Stats

Attention Stats

Abstract

Transgenic labeling of innate immune cell lineages within the larval zebrafish allows for real-time, in vivo analyses of microbial pathogenesis within a vertebrate host. To date, labeling of zebrafish macrophages has been relatively limited, with the most specific expression coming from the mpeg1 promoter. However, mpeg1 transcription at both endogenous and transgenic loci becomes attenuated in the presence of intracellular pathogens, including Salmonella typhimurium and Mycobacterium marinum. Here, we describe mfap4 as a macrophage-specific promoter capable of producing transgenic lines in which transgene expression within larval macrophages remains stable throughout several days of infection. Additionally, we have developed a novel macrophage-specific Cre transgenic line under the control of mfap4, enabling macrophage-specific expression using existing floxed transgenic lines. These tools enrich the repertoire of transgenic lines and promoters available for studying zebrafish macrophage dynamics during infection and inflammation and add flexibility to the design of future macrophage-specific transgenic lines.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0138949

Publication Info

Walton, Eric M, Mark R Cronan, Rebecca W Beerman and David M Tobin (2015). The Macrophage-Specific Promoter mfap4 Allows Live, Long-Term Analysis of Macrophage Behavior during Mycobacterial Infection in Zebrafish. PLoS One, 10(10). p. e0138949. 10.1371/journal.pone.0138949 Retrieved from https://hdl.handle.net/10161/10845.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Rebecca Beerman

Program Mgr, Clinical Data Mgmt
Tobin

David M. Tobin

Professor of Molecular Genetics and Microbiology

Tuberculosis: Mycobacterial Pathogenesis and Host Susceptibility

Tuberculosis kills 1.5 million people annually. Our laboratory aims to understand the intricate interplay between mycobacteria and their hosts using a combination of model organism genetics, human genetics, pharmacology and high-resolution microscopy. By identifying key pathways utilized by the infecting bacteria and the host innate immune system, we hope to discover new therapeutic targets and interventions to combat this enduringly destructive disease.

Using a Mycobacterium/zebrafish model, we have identified new host susceptibility loci for tuberculosis. Zebrafish are natural hosts to Mycobacterium marinum, the closest relative of the Mycobacterium tuberculosis complex. Because zebrafish embryos and larvae are optically transparent, we are able to visualize the complex details of mycobacterial pathogenesis in whole, live animals. The facile genetics of the zebrafish allow us to map and positionally clone affected host susceptibility genes. In addition, zebrafish larvae are remarkably permeable to small molecules, providing a platform for whole-animal pharmacological manipulation of specific host immune responses.

We have identified novel pathways that modulate susceptibility to tuberculosis. We have shown that genes identified in the zebrafish model are also important in human tuberculosis. We find robust associations of human variants in a specific eicosanoid pathway with susceptibility to both tuberculosis and leprosy.

We have active collaborations in both Vietnam and Guatemala. In Guatemala, we are working with the Clínica Familiar Luis Angel García and the Asociación de Salud Integral to support projects involving HIV-infected patients and to understand the dynamics of TB transmission in Central America.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.