Immune response and Coxiella burnetii invasion.

Coxiella burnetii, the causative agent of Q fever, has evolved a wealth of mechanisms in order to persist within hosts. Two tissues, namely adipose tissue and placenta, are candidates to house C. burnetii, but the mechanisms governing C. burnetii survival in these tissues are still unknown. In contrast, monocytes and macrophages are well-known targets of C. burnetii. First, C. burnetii has developed a specific strategy of phagocytosis subversion that consists of the inhibition of integrin interplay. Second, C. burnetii persistence is associated with macrophage activation profiles. Indeed, monocytes (in which C. burnetii survives without replication) exhibit a proinflammatory M1-type response, whereas macrophages (in which C. burnetii slowly replicates) are polarized towards an M2-type. Third, interleukin-10 produced by monocytes is a main factor of the chronic development of Q fever, and murine models confirm the key role of interleukin-10 in C. burnetii persistence. Fourth, apoptotic cells may play a key role in chronic Q fever. The uptake of apoptotic cells by circulating monocytes increases C. burnetii replication by redirecting monocytes toward a non-protective M2 profile. In the presence of interferon-γ, apoptotic cell engulfment is inhibited and monocytes polarized toward an M1 program are able to kill C. burnetii; this is the situation observed in patients with uncomplicated acute Q fever. Finally, we cannot exclude that regulatory T cells may play a role in C. burnetii persistence because their number is increased in patients with chronic Q fever.

The gene expression analysis of blood reveals S100A11 and AQP9 as potential biomarkers of infective endocarditis.

BACKGROUND: The diagnostic and prognostic assessments of infective endocarditis (IE) are challenging. To investigate the host response during IE and to identify potential biomarkers, we determined the circulating gene expression profile using whole genome microarray analysis. METHODS AND RESULTS: A transcriptomic case-control study was performed on blood samples from patients with native valve IE (n = 39), excluded IE after an initial suspicion (n = 10) at patient's admission, and age-matched healthy controls (n = 10). Whole genome microarray analysis showed that patients with IE exhibited a specific transcriptional program with a predominance of gene categories associated with cell activation as well as innate immune and inflammatory responses. Quantitative real-time RT-PCR performed on a selection of highly modulated genes showed that the expression of the gene encoding S100 calcium binding protein A11 (S100A11) was significantly increased in patients with IE in comparison with controls (P<0.001) and patients with excluded IE (P<0.05). Interestingly, the upregulated expression of the S100A11 gene was more pronounced in staphylococcal IE than in streptococcal IE (P<0.01). These results were confirmed by serum concentrations of the S100A11 protein. Finally, we showed that in patients with IE, the upregulation of the aquaporin-9 gene (AQP9) was significantly associated with the occurrence of acute heart failure (P = 0.02). CONCLUSIONS: Using transcriptional signatures of blood samples, we identified S100A11 as a potential diagnostic marker of IE, and AQP9 as a potential prognostic factor.