Whipple's Disease: a Macrophage Disease

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Macrophage polarization in bacterial infections

Converging studies have shown that M1 and M2 macrophages are functionally polarized in response to microorganisms and host mediators. Gene expression profiling of macrophages reveals that various Gramnegative and Gram-positive bacteria induce the transcriptional activity of a “common host response,” which includes genes belonging to the M1 program. However, excessive or prolonged M1 polarization can lead to tissue injury and contribute to pathogenesis. The so-called M2 macrophages play a critical role in the resolution of inflammation by producing antiinflammatory mediators. These M2 cells cover a continuum of cells with different phenotypic and functional properties. In addition, some bacterial pathogens induce specific M2 programs in macrophages. In this review

Human galectin-1 and galectin-3 promote Tropheryma whipplei

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Human galectin-1 and galectin-3 promote Tropheryma whipplei infection

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Tropheryma whipplei glycosylation in the pathophysiologic profile of Whipple's disease.

International audienceBACKGROUND: Tropheryma whipplei is a bacterium commonly found in people with Whipple's disease, a rare systemic chronic infection. In the present study, we hypothesized that bacterium glycosylation may impair the immune response. METHODS: Bacterial extracts were analyzed by glycostaining, and reactive proteins, identified by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectometry, were purified to generate antibodies that could be used in immunofluorescence studies. The reactivity of serum samples obtained from patients and asymptomatic carriers was tested against native or deglycosylated bacteria, for which the fate in macrophages was also investigated. RESULTS: To our knowledge, we evidenced, for the first time in T. whipplei, a 110-kDa glycoprotein containing sialic acid. This protein, identified as an Wnt1-inducible signaling pathway (WiSP) protein, is associated with periodic acid-Schiff (PAS) staining in infected intramacrophage biofilm. Consistent with the lack of enzymes required for the glycosylation pathway in this bacterium, the glycoproteins disappear during in vitro axenic subcultures, whereas human transcriptome analysis reveals the up-regulation of corresponding genes within infected macrophages. Proteic antigens are not recognized by the serum samples obtained from patients compared with those obtained from nonsick carriers, and T. whipplei that exhibits a low glycosylation profile does not efficiently multiply in macrophages in vitro. CONCLUSIONS: T. whipplei glycosylation is likely to impair antibody-mediated immune recognition in patients. Such an intracellular antigen masking system in bacteria has not previously been described

Differential oxidative damage and expression of stress defence regulons in culturable and non-culturable Escherichia coli cells

Potentially pathogenic bacteria, such as Escherichia coli and Vibrio cholerae, become non-culturable during stasis. The analysis of such cells has been hampered by difficulties in studying bacterial population heterogeneity. Using in situ detection of protein oxidation in single E. coli cells, and using a density-gradient centrifugation technique to separate culturable and non-culturable cells, we show that the proteins in non-culturable cells show increased and irreversible oxidative damage, which affects various bacterial compartments and proteins. The levels of expression of specific stress regulons are higher in non-culturable cells, confirming increased defects relating to oxidative damage and the occurrence of aberrant, such as by amino-acid misincorporation, proteins. Our data suggest that non-culturable cells are produced due to stochastic deterioration, rather than an adaptive programme, and pinpoint oxidation management as the 'Achilles heel' of these cells