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

Abstract

Summary 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.

Th1 cytokines, true functional signatures for protective immunity against TB?

“…Lazar-Molnar et al 60 Barber et al 61 Fujita K et al 62 Sakai et al 63 Th1 cytokines and TB G Zeng et al Guerra-Laso et al 64 Che et al 65 Wareham et al 66 IL-7/15 ELISA, cytometric bead assay Enhanced Mtb survival was shown in IL-7-or IL-15-treated mice.…”

Interleukin-26: An Emerging Player in Host Defense and Inflammation

“…The involvement of IL-26 in host defense against intracellular bacteria has also been indicated [22] . A recent study described the potential role of IL-26 infection with Mycobacterium tuberculosis in isolated human blood monocytes cultured in vitro [22].…”

“…A recent study described the potential role of IL-26 infection with Mycobacterium tuberculosis in isolated human blood monocytes cultured in vitro [22]. By screening for altered gene expression with microarray analysis, it was discovered that the IL-26 gene was downregulated in monocytes from tuberculosis patients.…”

Bringing in the Cavalry: IL-26 Mediates Neutrophil Recruitment to the Lungs

“…Given its expression by both hematopoietic and nonhematopoietic cells, and its role as a mediator of inflammation and protection against invading pathogens, the role of IL-26 at the lung mucosal surface is of great interest. Very little is known of IL-26 expression in the lungs, although one recent publication has shown an association between lower levels of IL-26 expression in serum of patients with tuberculosis (8). Interestingly, in monocytes infected with Mycobacterium tuberculosis, treatment with IL-26 inhibited M. tuberculosis killing, based on which IL-26 has been considered a "candidate gene for tuberculosis susceptibility" (8).…”