Microarray analysis of Mycobacterium tuberculosis-infected monocytes reveals IL26 as a new candidate gene for tuberculosis susceptibility.

Differences in the activity of monocytes/macrophages, important target cells of Mycobacterium tuberculosis, might influence tuberculosis progression. With the purpose of identifying candidate genes for tuberculosis susceptibility we infected monocytes from both healthy elderly individuals (a tuberculosis susceptibility group) and elderly tuberculosis patients with M. tuberculosis, and performed a microarray experiment. We detected 78 differentially expressed transcripts and confirmed these results by quantitative PCR of selected genes. We found that monocytes from tuberculosis patients showed similar expression patterns for these genes, regardless of whether they were obtained from younger or older patients. Only one of the detected genes corresponded to a cytokine: IL26, a member of the interleukin-10 (IL-10) cytokine family which we found to be down-regulated in infected monocytes from tuberculosis patients. Non-infected monocytes secreted IL-26 constitutively but they reacted strongly to M. tuberculosis infection by decreasing IL-26 production. Furthermore, IL-26 serum concentrations appeared to be lower in the tuberculosis patients. When whole blood was infected, IL-26 inhibited the observed pathogen-killing capability. Although lymphocytes expressed IL26R, the receptor mRNA was not detected in either monocytes or neutrophils, suggesting that the inhibition of anti-mycobacterial activity may be mediated by lymphocytes. Additionally, IL-2 concentrations in infected blood were lower in the presence of IL-26. The negative influence of IL-26 on the anti-mycobacterial activity and its constitutive presence in both serum and monocyte supernatants prompt us to propose IL26 as a candidate gene for tuberculosis susceptibility.

[Estimate of the real incidence of tuberculosis in the Leon Health Area: application of the capture-recapture method to compare two information sources]. / Aproximación a la incidencia real de tuberculosis en el Área de Salud de León: aplicación del método captura-recaptura para comparar 2 fuentes de información.

INTRODUCTION: The actual incidence of tuberculosis is probably higher than that previously published in national and international records. Under-reporting is estimated to fluctuate between 7% and 27%, according to studies. OBJECTIVE: To estimate the incidence rate of tuberculosis in the area of León for 2008 and 2009 using the capture-recapture method in order to compare two sources of information: prescribed tuberculostatic drugs (combination of rifampicin-isoniazid) and the regional epidemiological surveillance system register (SIVE). METHOD: Retrospective descriptive study in an area of 351,086 inhabitants of tuberculosis cases using as sources: (i), information on prescribed tuberculostatic drugs, and (ii), the SIVE register. We calculated incidence rates for each source by the capture-recapture method. We analyzed epidemiological and demographic data, symptoms, diagnosis, treatment and follow-up. RESULTS: The incidence based on the SIVE data for 2008 was 18.80/100,000 inhabitants and according to the pharmacy register, the rate was 26.77. The estimated value for 2009 based on the SIVE data was 18.23/100,000 inhabitants, and according to the pharmacy register, it was 22.50. After applying the capture-recapture method, the annual incidence for 2008 was 44.14/100,000 (95% CI; 37.88-50.41) and for 2009, it was 34.17/100,000 (95% CI; 30.19-38.17). In the study of all these years we have found that the number of cases were higher in the pharmacy register than the SIVE one. CONCLUSIONS: The SIVE data on the incidence of tuberculosis in our study area underestimates the actual incidence rate. The source of information that involves case record of tuberculosis in the community is under-used. The capture-recapture method is a good alternative to measure the incidence of tuberculosis, and to check the surveillance systems.

Immunological response to Mycobacterium tuberculosis infection in blood from type 2 diabetes patients.

The convergence of tuberculosis and diabetes represents a co-epidemic that threatens progress against tuberculosis. We have investigated type 2 diabetes as a risk factor for tuberculosis susceptibility, and have used as experimental model whole blood infected in vitro with Mycobacterium tuberculosis. Blood samples from diabetic patients were found to have a higher absolute neutrophil count that non-diabetic controls, but their immune functionality seemed impaired because they displayed a lower capacity to phagocytose M. tuberculosis, a finding that had been previously reported only for monocytes. In contrast, an increased production of TNFα was detected in infected blood from diabetic patients. Despite the altered phagocytic capacity showed by cells from these patients, the antimicrobial activity measured in both whole blood and monocyte derived macrophages was similar to that of controls. This unexpected result prompts further improvements in the whole blood model to analyze the immune response of diabetes patients to tuberculosis.

In vitro infection with Mycobacterium tuberculosis induces a distinct immunological pattern in blood from healthy relatives of tuberculosis patients.

Part of the susceptibility to tuberculosis has a genetic basis, which is clear in primary immunodeficiencies, but is less evident in apparently immunocompetent subjects. Immune responses were analysed in blood samples from tuberculosis patients and their healthy first-degree relatives who were infected in vitro with mycobacteria (either Mycobacterium tuberculosis or M. bovis BCG). The antimicrobial activity against M. tuberculosis in blood from relatives was significantly lower than that observed in healthy controls. Tuberculosis patients exhibited a higher number of neutrophils, and monocyte phagocytosis was inhibited in both relatives and tuberculosis patients. A remarkable finding was that the production of reactive oxygen species by infected neutrophils was higher in relatives than in healthy controls. A higher production of TNFα in infected blood from relatives was also observed. These results may indicate that relatives display a stronger inflammatory response and that their immune response to M. tuberculosis is different from those of unrelated controls. First-degree relatives may represent a highly informative group for the analysis of tuberculosis susceptibility.