We demonstrated that the Mycobacterium tuberculosis cell wall component lipoarabinomannan (LAM) is a very potent inducer of IL-1 beta gene expression in human monocytes and investigated the mechanism of this effect.
We conclude that BAL cells, especially alveolar macrophages, are activated in the alveolar inflammation of active TB and spontaneously release increased quantities of IL-1 beta, IL-6, and TNF-alpha, and that these cytokines are likely to be involved in directing granuloma formation and control of M. tuberculosis infection.
Thus, the polymorphism at the IL-1 locus influences the cytokine response and may be a determinant of delayed-type hypersensitivity and disease expression in human tuberculosis.
From a wealth of rodent studies using live infection models, the following conclusions can be drawn: (1) neutralization or gene deletion for TNF-alpha is frequently associated with reduction of host defense in models of live Gram-positive or Gram-negative infections as well as infection by intracellular microbes such as Salmonella and Listeria; (2) absence of the IL-1 receptor can also result in decreased resistance to Listeria or Gram-positive bacteria and (3) TNF-alpha and IFN-gamma are required for defense against infection caused by Mycobacterium tuberculosis.
To better characterize the host genetic factors determining the susceptibility to TB, we evaluated the influence of functional polymorphisms in IL1B, TAP and IKBL genes on the risk of developing pulmonary TB in a Northwestern Colombian population, an endemic area of M. tuberculosis infection.
Although Rv1813c is not required for survival of M. tuberculosis in vitro, including under conditions in which MprAB and DosRST signaling are activated, an M. tuberculosis ΔRv1813c mutant is attenuated in the low-dose aerosol model of murine tuberculosis, where it exhibits a lower bacterial burden, delayed time to death, and decreased ability to stimulate proinflammatory cytokines interleukin-1β (IL-1β) and IL-12.
HHC with CC (P < 0.03, OR = 1.833 and 95% CI = 1.1-3.35) genotype in IL-1β and GA (P < 0.0001, OR = 4.612 and 95% CI = 2.225-9.702) genotype in IL-10 were at increased risk of developing tuberculosis.
The central proteins for protection against tuberculosis are attributed to interferon-γ, tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, while IL-10 primarily suppresses anti-mycobacterial responses.
Secretion of TNF-α and IL-1β by Mtb-infected macrophages promotes necrosis, and this deregulation of cell death pathways may favor the release of viable bacilli, thus leading to the progression of tuberculosis.
These observations support a specific role for IL-1β and granulocytic inflammation as a driver of TB disease progression in humans, and suggest novel strategies for the prevention and treatment of tuberculosis.
Most of the host components involved in TB inflammation, including cytokines (interferons, interleukin (IL)-1, IL-10, tumour necrosis factor) and cells (neutrophils, macrophages, regulatory T cells, type 1 helper lymphocytes, pneumocytes), exhibit dual features: they foster or repress local inflammatory events.
We systematically searched published literatures on IL-1β gene and IL-6 gene polymorphisms and tuberculosis risk by the PubMed, Medline, Embase, Web of Science, Elsevier Science Direct and Cochrane Library databases, and identified outcome data from all articles.
Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB.