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In vitro studies on extracellular matrix production by M.leprae infected murine neurofibroblasts
N Singh1, T J Birdi, S Chandrashekar
1Foundation for Medical Research, R.G. Thadani Marg, Bombay, India.
Abstract:
Fibroblasts and a host of macrophage secretory products have been implicated in a number of diseases where excess extracellular matrix (ECM) deposition is the main pathological feature. Fibrosis characterized by excessive deposition of collagen also contributes to the irreversible nerve damage observed in leprosy. Since M. leprae are seen within neurofibroblasts (Nf) in the advanced stages of the disease and macrophages form a common infiltrating cellular constituent of leprous nerves at all stages, secretion of ECM proteins by Nf was studied, in vitro following infection with M. leprae and in the presence of macrophage secretory products. These studies were compared in cells derived from two strains of mice, Swiss White (SW) and C57BL/6, as they differ in their response to M. leprae infection and parallel those observed in lepromatous and tuberculoid patients, respectively. On infection with M. leprae, Nfs showed a decrease in secretion of collagen type IV in SW and type I in C57Bl/6 strain. Macrophages caused a further decrease in the secretion of collagen types affected by M. leprae infection per se, while the other collagen types, viz. I and III in SW strain and III and IV in C57Bl/s strain, were unaffected. This study indicates that neural collagenization in nerves in advanced leprosy may be of Nf origin. However, unlike other diseases with excess collagen deposition, ECM proteins produced by Nfs in response to nerve damage may not be of prime importance in the progression of leprous neuropathy and occur as a general response to loss of cellular content in leprous nerves.
Insights
Leprosy nerve damage involves collagen deposition from neurofibroblasts (Nf). Macrophage products further alter extracellular matrix (ECM) protein secretion, but may not drive neuropathy progression.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Excess extracellular matrix (ECM) deposition, particularly collagen, is a hallmark of fibrotic diseases and contributes to nerve damage in leprosy.
- Leprosy involves Mycobacterium leprae (M. leprae) within neurofibroblasts (Nf) and macrophages in affected nerves.
Purpose of the Study:
- To investigate the secretion of ECM proteins by Nf in vitro following M. leprae infection and in the presence of macrophage secretory products.
- To compare these effects in two mouse strains (Swiss White and C57BL/6) that exhibit differential responses to M. leprae, mirroring human leprosy types.
Main Methods:
- In vitro culture of Nf from Swiss White and C57BL/6 mice.
- Infection of Nf with M. leprae.
- Treatment of Nf with macrophage secretory products.
- Quantification of ECM protein secretion, including collagen types I, III, and IV.
Main Results:
- M. leprae infection decreased collagen type IV secretion in SW Nf and collagen type I in C57BL/6 Nf.
- Macrophage products further reduced secretion of the affected collagen types.
- Other collagen types remained largely unaffected by M. leprae or macrophage products.
Conclusions:
- Neural collagenization in advanced leprosy may originate from Nf.
- ECM protein production by Nf might be a general response to cellular loss rather than a primary driver of leprous neuropathy.