A protective role for eosinophils in host resistance to Mycobacterium tuberculosis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE165871 | GEO | 2021/08/01
REPOSITORIES: GEO
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Project description:Every year, tuberculosis kills nearly 1.8 million people through out the world. Though outcome of M. tuberculosis infection into active disease is determined by the host and bacterial factors, a strong host immune response controls the growth of the bacilli effectively. However, in a host with suboptimal immune response, the bacilli grows and mounts active disease. Activation of immune response following M. tuberculosis infection affects the expression of many host genes that are involved in the production of immune system molecules such as cytokines, chemokines, surface receptors and transcriptional regulators that manifest in the change of subsequent cellular events, including activation, maturation, chemotaxis and proliferation of effector cells. However, the specific nature of the host-pathogen interactions and the outcome of Mtb infection are not fully understood. In this study, we have analysed the systematic changes in the global host gene expression profile in the lungs of Mtb infected rabbits at various stages of infection. Mtb infected rabbit lung tissues were isolated at T=0,2, 4 and 16 weeks post-infection. Lung bacterial load, histologic changes and host and bacterial gene expression were determined for each timepoint and compared . Our data suggests a strong correlation between the significant changes in the global transcriptome of infected rabbits and the progression of Mtb infection into a chronic, cavitary TB disease. The microarray experiments involves comparison of: 1) Changes in rabbit gene expression between Mtb-HN878 infected and uninfected animals at 2,4 and 16 weeks post infection. New Zealand White rabbits were infected with Mtb HN878 at 3.2log10 (on day 0). Lung tissue from Mtb-infected rabbits were isolated at Day0, 2, 4 and 16 weeks post infection and used for total RNA extraction.
2011-12-07 | E-GEOD-33094 | biostudies-arrayexpress
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Project description:Mycobacterium tuberculosis infection (Mtb) is the leading cause of death due to a single infectious agent and among the top ten causes of all human death worldwide1. CD4 T cells are essential for resistance to Mtb infection, and for decades it has been thought that IFN production is the primary mechanism of CD4 T cell-mediated protection2,3. However, IFN responses do not correlate with host protection, and several reports have demonstrated that additional anti-tuberculous CD4 T cell effector functions remain unaccounted for4-8. Here we show that the TNF superfamily molecule CD153 (TNFSF8) is required for IFN-independent control of pulmonary Mtb infection by CD4 T cells. In Mtb infected mice, CD153 expression is highest on Ag-specific Th1 cells in the lung tissue parenchyma, but its induction does not require Th1 polarization. CD153 deficient mice develop high pulmonary but not splenic bacterial loads and succumb early to Mtb infection. Reconstitution of T cell-deficient hosts with either CD153-/- or IFN-/- CD4 T cells fails to rescue mice from early mortality, but reconstitution with a mixture of CD153-/- and IFN-/- CD4 T cells provides similar protection as WT T cells. In Mtb infected non-human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the airways compared to the blood, and the frequency of Mtb-specific CD153-expressing CD4 T cells inversely correlates with bacterial loads in granulomas. In Mtb infected humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells that are much more abundant in individuals with controlled latent Mtb infection compared to those with active TB. In all three species, Mtb-specific CD8 T cells did not upregulate CD153 following peptide stimulation. Thus, we have identified expression of CD153 by CD4 T cells as a major immune mechanism of host protection against pulmonary Mtb infection.
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Project description:Every year, tuberculosis kills nearly 1.8 million people through out the world. Though outcome of M. tuberculosis infection into active disease is determined by the host and bacterial factors, a strong host immune response controls the growth of the bacilli effectively. However, in a host with suboptimal immune response, the bacilli grows and mounts active disease. Activation of immune response following M. tuberculosis infection affects the expression of many host genes that are involved in the production of immune system molecules such as cytokines, chemokines, surface receptors and transcriptional regulators that manifest in the change of subsequent cellular events, including activation, maturation, chemotaxis and proliferation of effector cells. However, the specific nature of the host-pathogen interactions and the outcome of Mtb infection are not fully understood. In this study, we have analysed the systematic changes in the global host gene expression profile in the lungs of Mtb infected rabbits at various stages of infection. Mtb infected rabbit lung tissues were isolated at T=0,2, 4 and 16 weeks post-infection. Lung bacterial load, histologic changes and host and bacterial gene expression were determined for each timepoint and compared . Our data suggests a strong correlation between the significant changes in the global transcriptome of infected rabbits and the progression of Mtb infection into a chronic, cavitary TB disease. The microarray experiments involves comparison of: 1) Changes in rabbit gene expression between Mtb-HN878 infected and uninfected animals at 2,4 and 16 weeks post infection.
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