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Brucella melitensis, B. neotomae and B. ovis elicit common and distinctive macrophage defense transcriptional responses. Exp Biol Med (Maywood) 2009 Dec;234(12):1450-67

Date

11/26/2009

Pubmed ID

19934366

Pubmed Central ID

PMC2880867

DOI

10.3181/0904-RM-124

Scopus ID

2-s2.0-72449175964   26 Citations

Abstract

Brucella spp. establish an intracellular replicative niche in macrophages, while macrophages attempt to eliminate the bacteria by innate defense mechanisms. Brucella spp. possess similar genomes yet exhibit different macrophage infections. Few B. melitensis and B. neotomae enter macrophages with intracellular adaptation occurring over 4-8 hr. Conversely, B. ovis are readily ingested by macrophages and exhibit a persistent plateau of infection. Evaluating early macrophage interaction with Brucella spp. allows discovery of host entry and intracellular translocation mechanisms. Microarray analysis of macrophage transcriptional response following a 4 hr infection by different Brucella spp. revealed common macrophage genes altered in expression compared to uninfected macrophages. Macrophage infection with three different Brucella spp. provokes a common innate immune theme with increased transcript levels of chemokines and defense response genes and decreased transcript levels of GTPase signaling and cytoskeletal function that may affect trafficking of Brucella containing vesicles. For example, transcript levels of genes associated with chemotaxis (IL-1beta, MIP-1alpha), cytokine regulation (Socs3) and defense (Fas, Tnf) were increased, while transcript levels of genes associated with vesicular trafficking (Rab3d) and lysosomal associated enzymes (prosaposin) were decreased. Genes with altered macrophage transcript levels among Brucella spp. infections may correlate with species specific host defenses and intracellular survival strategies. Depending on the infecting Brucella species, gene ontology categorization identified genes differentially involved in cell growth and maintenance, endopeptidase inhibitor activity and G-protein mediated signaling. Examples of decreased gene expression in B. melitensis infection but not other Brucella spp. were growth arrest (Gas2), immunoglobulin receptor (FcgammarI) and chemokine receptor (Cxcr4) genes, suggesting opposing effects on intracellular functions.

Author List

Covert J, Mathison AJ, Eskra L, Banai M, Splitter G

Author

Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brucella melitensis
Brucella ovis
Brucellosis
Cell Line
Chemotaxis
Cytokines
Gene Expression Profiling
Gene Expression Regulation
Immunity, Innate
Macrophages
Mice
Microfilament Proteins
Oligonucleotide Array Sequence Analysis
Receptors, CXCR4
Receptors, IgG
Signal Transduction
Species Specificity
Transcription, Genetic