Brucella Control of Dendritic Cell Maturation Is Dependent on the TIR-Containing Protein Btp1

Abstract

Brucella is an intracellular pathogen able to persist for long periods of time within the host and establish a chronic disease. We show that soon after Brucella inoculation in intestinal loops, dendritic cells from ileal Peyer's patches become infected and constitute a cell target for this pathogen. In vitro, we found that Brucella replicates within dendritic cells and hinders their functional activation. In addition, we identified a new Brucella protein Btp1, which down-modulates maturation of infected dendritic cells by interfering with the TLR2 signaling pathway. These results show that intracellular Brucella is able to control dendritic cell function, which may have important consequences in the development of chronic brucellosis.

The identification of wadB, a new glycosyltransferase gene, confirms the branched structure and the role in virulence of the lipopolysaccharide core of Brucella abortus

“…As a control, we used a virB10 mutant (Table 1) defective in the Type IV secretion system required for normal intracellular trafficking and multiplication. As expected [20,29] , and regardless of the strain, the vast majority of infected BMDCs contained less than 10 bacteria at 2 h post-infection ( Figure 3A). At 48 h post-infection, the proportion of BMDCs containing more than 10 bacteria increased for Ba-parental but not for the virB10 GFP mutant, as expected from their respective virulent and attenuated phenotype [6].…”

“…abortus is characteristically able to multiply in dendritic cells [29]. To study the behavior of BaΔwadB in these cells, we infected C57BL/6 BMDC with BaΔwadB, BaΔwadC and Ba-parental, and scored the number of intracellular bacteria in infected MHCII positive cells at 2 and 48 h post-infection.…”

A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors

“…As bacterial TIR proteins down‐modulate NF‐κB activation (Newman et al , 2006; Cirl et al , 2008; Salcedo et al , 2008, 2013; Spear et al , 2012; Askarian et al , 2014; Zou et al , 2014), we infected the lung carcinoma epithelial cell line A549, a well‐established cellular model for Pseudomonas infection and analysed NF‐κB translocation into the nucleus after one hour of infection by confocal microscopy. We developed an automated analysis of p65/RelA fluorescence in relation to DAPI labelling using a specific ImageJ plugin from images obtained by confocal microscopy (Fig EV1A) which allowed us to clearly differentiate between TNFα‐treated and mock‐infected cells (Figs 2A and EV1B).…”

“…Bacterial targeting of TLRs has been best described for uropathogenic E. coli TcpC (Cirl et al , 2008) and Brucella BtpA, also known as TcpB (Cirl et al , 2008; Salcedo et al , 2008), even though their molecular mode of action remains elusive. Brucella relies on an additional TIR protein, BtpB to down‐modulate inflammation during infection (Salcedo et al , 2013).…”

“…In contrast, few examples of direct blocking at the level of initial receptor–adaptor complexes are known. Some bacterial pathogens rely on TIR domain‐containing proteins to perturb TIR‐dependent interactions (Newman et al , 2006; Cirl et al , 2008; Salcedo et al , 2008, 2013), essential in innate immune signalling. The growing number of bacterial TIR proteins recently identified in both Gram‐negative and Gram‐positive human pathogens (Spear et al , 2012; Askarian et al , 2014; Zou et al , 2014) highlights the importance of this immune evasion strategy in disease.…”