In vivo expression of innate immunity markers in patients with mycobacterium tuberculosis infection

Abstract

BackgroundToll-like receptors (TLRs), Coronin-1 and Sp110 are essential factors for the containment of Mycobacterium tuberculosis infection. The purpose of this study was to investigate the in vivo expression of these molecules at different stages of the infection and uncover possible relationships between these markers and the state of the disease.MethodsTwenty-two patients with active tuberculosis, 15 close contacts of subjects with latent disease, 17 close contacts of subjects negative for mycobacterium antigens and 10 healthy, unrelated to patients, subjects were studied. Quantitative mRNA expression of Coronin-1, Sp110, TLRs-1,-2,-4 and -6 was analysed in total blood cells vs an endogenous house-keeping gene.ResultsThe mRNA expression of Coronin-1, Sp110 and TLR-2 was significantly higher in patients with active tuberculosis and subjects with latent disease compared to the uninfected ones. Positive linear correlation for the expression of those factors was only found in the infected populations.ConclusionsOur results suggest that the up-regulation of Coronin-1 and Sp110, through a pathway that also includes TLR-2 up-regulation may be involved in the process of tuberculous infection in humans. However, further studies are needed, in order to elucidate whether the selective upregulation of these factors in the infected patients could serve as a specific molecular marker of tuberculosis.

Natural Killer Cell Activation Distinguishes Mycobacterium tuberculosis–Mediated Immune Reconstitution Syndrome From Chronic HIV and HIV/MTB Coinfection

“…It is possible that the observed NK cell activation may result in part from their interaction with mycobacterial products (e.g. via TLR2, 36 ), as well as from enhanced chemokines production by infected/bystander macrophages at the sites of infection. Our observation that IL-8 is significantly increased is uTB-IRIS further supports this model, suggesting that IL-8 might be involved in the activation and chemotaxis of NK cells expressing CXCR1 37 or CXCR2 35 .…”

Are mouse models of human mycobacterial diseases relevant? Genetics says: ‘yes!’

“…A recent study of patients with TB and healthy controls in China claims significant associations between a few SP110 SNP and elevated incidence of TB; 64 however, the statistical details of this work, published in Chinese, are unclear. Although expression of SP110 mRNA in peripheral blood cells was found to be higher in patients with TB than in healthy controls, 65 the most likely explanation for this effect is up‐regulation of the expression because of elevated IFN‐γ levels in infected individuals, 59,62 rather than genuine genetic association. A supportive evidence of the role of SP110 in mycobacterial infections control was provided by the study in cattle, in which a single SNP in the bovine SP110 orthologue was associated with the difference in susceptibility to John’s disease, a chronic granulomatous condition caused by M. avium ssp.…”

Tuberculosis-resistant transgenic cattle

“…Expression of an Ipr1 (SP110) transgene in susceptible mice improved their resistance to M. tuberculosis as well as Listeria (7), and with the results of Wu et al (1), implies a correlation between SP110 expression and TB resistance. However, higher expression of SP110 mRNA was found in patients with active or latent TB compared with naive groups (15). Wu et al…”