Using freshly resected lung tissue from 21 patients and two distinct mouse models, tuberculosis researchers have identified a protein that plays an essential role in host defense against this deadly disease.
The researchers were able to separate different types of cells found in distinct niches of human freshly resected TB lungs and characterize those cells for production of the protein heme oxygenase-1. Heme oxygenase-1, or HO-1, is an enzyme that protects cells from harmful reactive oxygen or nitrogen intermediates; HO-1 also is able to control inflammatory responses.
The researchers found that HO-1 in human TB lungs was expressed primarily by myeloid immune cells, including neutrophils and macrophages, and that HO-1 levels in these cells were directly proportional to protection against TB pathophysiology.
Specifically, there was a greater percentage of HO-1-producing neutrophils and macrophages in uninfected areas of the lung than in diseased areas, and those cells in uninfected areas produced more HO-1 than the cells in diseased areas. As a consequence, the lack of HO-1 protection in diseased areas allowed myeloid cell-production of destructive reactive oxygen and nitrogen species. What makes these findings clinically relevant is that HO-1 is essential in humans but not in mice, which points to the importance of examining human TB lung tissue to complement animal models for TB.
This finding in humans was supported by two HO-1 deficient mouse models that showed HO-1 is necessary to control myeloid cell infiltration and inflammation to protect against TB progression. One mouse model was a global knockout of the HO-1 gene; the other model was an HO-1 knockout in myeloid cells only. In both models, knockout mice had more susceptibility to Mtb infection -- the knockout mice died sooner and had higher loads of Mtb in their lungs and spleens. The knockout mice also had increased infiltration of immune cells and levels of cytokines, the cell-signaling proteins that regulate or stimulate immune responses.
Overall, the findings from human lungs and the mouse models showed that expression of HO-1, especially within myeloid cells, appears to be essential for host defense against Mtb disease progression. For human TB patients, the senior author says, the research suggests that finding a way to upregulate HO-1 activity might limit immunopathology during active TB disease. This research was published in the journal Cell Reports.
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31677-2
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
'Jumping genes' drive many cancers
Read more
Gene duplications could be fixed with CRISPR/CAS9 and MMEJ repair m…
Read more
Normal mutations in human livers can promote tissue regeneration
Read more
Poverty leaves a mark on our genes
Read more
ALS progression at the genetic and cellular level
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar