Brucella alters the immune response in a prpA-dependent manner

Spera, Juan Manuel; Comerci, Diego J.; Ugalde, Juan Esteban

doi:10.1016/j.micpath.2014.01.003

Cited by 19 publications

(17 citation statements)

References 37 publications

(38 reference statements)

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“…B-cell proliferation is initiated by the secretion of Brucella virulence factor prpA that interact with macrophages and release several soluble factors necessary for establishing chronic infection (Spera et al, 2006 , 2013 ). In addition to this, Brucella change the cytokine level of IFN-γ, TNF-α, IL-10 and TGFβ1 in the early stages of brucellosis in a prpA dependent manner (Spera et al, 2014 ). Recent studies clarify the roles of Btp1/TcpB, Br-LPS and PrpA as being significant immunomodulatory molecules with the ability to interplay with host immune mechanisms.…”

Section: Brucella Impressive Mechanisms To Evade Adaptive Immentioning

confidence: 99%

Establishment of Chronic Infection: Brucella's Stealth Strategy

Waqas

Zheng

Liu

2016

Front. Cell. Infect. Microbiol.

108

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Brucella is a facultative intracellular pathogen that causes zoonotic infection known as brucellosis which results in abortion and infertility in natural host. Humans, especially in low income countries, can acquire infection by direct contact with infected animal or by consumption of animal products and show high morbidity, severe economic losses and public health problems. However for survival, host cells develop complex immune mechanisms to defeat and battle against attacking pathogens and maintain a balance between host resistance and Brucella virulence. On the other hand as a successful intracellular pathogen, Brucella has evolved multiple strategies to evade immune response mechanisms to establish persistent infection and replication within host. In this review, we mainly summarize the “Stealth” strategies employed by Brucella to modulate innate and the adaptive immune systems, autophagy, apoptosis and possible role of small noncoding RNA in the establishment of chronic infection. The purpose of this review is to give an overview for recent understanding how this pathogen evades immune response mechanisms of host, which will facilitate to understanding the pathogenesis of brucellosis and the development of novel, more effective therapeutic approaches to treat brucellosis.

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Section: Brucella Impressive Mechanisms To Evade Adaptive Immentioning

confidence: 99%

Establishment of Chronic Infection: Brucella's Stealth Strategy

Waqas

Zheng

Liu

2016

Front. Cell. Infect. Microbiol.

108

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“…To achieve this, the bacterium has the capacity to translocate to the host cells a plethora of proteins that alter either the normal trafficking of the intracellular bacteria or the immune response triggered by the infection (3,10). PrpA is one of these effector proteins, and we have previously shown that this virulence factor is involved in the modulation of the immune response, acting on macrophages and triggering a polyclonal B-cell proliferation response that allows the bacterium to establish a persistent infection (5)(6)(7). How the protein is targeted to the plasma membrane of the host cell after its translocation from the Brucella-containing vacuole has not been elucidated until now.…”

Section: Discussionmentioning

confidence: 99%

“…Immunoglobulin quantification. The titers of specific immunoglobulins against Brucella were determined by indirect enzyme-linked immunosorbent assay (ELISA) (6). Briefly, ELISA MaxiSorp plates (Nunc, USA) were sensitized with 0.4 g/well of Brucella abortus total protein extracts overnight and blocked for 2 h with 1% BSA in PBS.…”

Section: Methodsmentioning

confidence: 99%

“…One example of the last type of modulation is the one triggered by PrpA (for proline racemase protein A), a protein of Brucella that our group has identified and characterized as a polyclonal B-cell mitogen involved in the establishment of the chronic phase of the infectious process in mice (5). PrpA is a strong immune modulator as it induces B-cell proliferation in vitro and in vivo, T-cell anergy, and alteration of the cytokine pattern and humoral immune response during infection (6). Interestingly, even though PrpA induces polyclonal B-cell proliferation, its cellular target is actually macrophages.…”

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confidence: 99%

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Brucella Hijacks Host-Mediated Palmitoylation To Stabilize and Localize PrpA to the Plasma Membrane

et al. 2018

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are a group of pathogenic intracellular bacteria with the ability to modulate the host response, both at the individual cell level and systemically. One of the hallmarks of the virulence process is the capacity of the bacteria to downregulate the adaptive and acquired host immune response through a plethora of virulence factors that directly impact several key signaling cascades. PrpA is one of those virulence factors that alters, via its polyclonal B-cell activity, the humoral and cellular immune responses of the host, ultimately favoring the establishment of a chronic infection. Even though PrpA affects B cells, it directly targets macrophages, triggering a response that ultimately affects B lymphocytes. In the present article we report that PrpA is S-palmitoylated in two N-terminal cysteine residues by the host cell and that this modification is necessary for its biological activity. Our results demonstrate that S-palmitoylation promotes PrpA migration to the host cell plasma membrane and stabilizes the protein during infection. These findings add a new mechanism exploited by this highly evolved pathogen to modulate the host immune response.

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“…Brucellaceae are wide spread zoonotic intracellular pathogens with the capacity to evade and modulate the immune response of the infected hosts, a hallmark of their infectious processes [1]. Many of these immunomodulatory activities are achieved by a plethora of virulence factors that are able to manipulate the immune system to its benefit, promoting bacterial proliferation and the establishment of the chronic infectious phase [2][3][4][5][6][7]. Brucella is considered a pathogen with a stealthy strategy, meaning that is able to avoid a strong immune response "hiding" its pathogen-associated molecular patterns (PAMPs).…”

Section: Introductionmentioning

confidence: 99%

RomA, A Periplasmic Protein Involved in the Synthesis of the Lipopolysaccharide, Tunes Down the Inflammatory Response Triggered by Brucella

Valguarnera

Spera

Czibener

et al. 2018

The Journal of Infectious Diseases

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Brucellaceae are stealthy pathogens with the ability to survive and replicate in the host in the context of a strong immune response. This capacity relies on several virulence factors that are able to modulate the immune system and in their structural components that have low proinflammatory activities. Lipopolysaccharide (LPS), the main component of the outer membrane, is a central virulence factor of Brucella, and it has been well established that it induces a low inflammatory response. We describe here the identification and characterization of a novel periplasmic protein (RomA) conserved in alpha-proteobacteria, which is involved in the homeostasis of the outer membrane. A mutant in this gene showed several phenotypes, such as membrane defects, altered LPS composition, reduced adhesion, and increased virulence and inflammation. We show that RomA is involved in the synthesis of LPS, probably coordinating part of the biosynthetic complex in the periplasm. Its absence alters the normal synthesis of this macromolecule and affects the homeostasis of the outer membrane, resulting in a strain with a hyperinflammatory phenotype. Our results suggest that the proper synthesis of LPS is central to maximize virulence and minimize inflammation.

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Brucella alters the immune response in a prpA-dependent manner

Cited by 19 publications

References 37 publications

Establishment of Chronic Infection: Brucella's Stealth Strategy

Establishment of Chronic Infection: Brucella's Stealth Strategy

Brucella Hijacks Host-Mediated Palmitoylation To Stabilize and Localize PrpA to the Plasma Membrane

RomA, A Periplasmic Protein Involved in the Synthesis of the Lipopolysaccharide, Tunes Down the Inflammatory Response Triggered by Brucella

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