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Optimized Protocols for Mycobacterium leprae Strain Management: Frozen Stock Preservation and Maintenance in Athymic Nude Mice
Published on: March 23, 2014
Emergence of an effective adaptive cell mediated immune response to Mycobacterium leprae is not impaired in reactive
Deanna A Hagge1, Vilma T Marks, Nashone A Ray
1Immunology Research Department, National Hansen's Disease Programs, Laboratory Research Branch, Baton Rouge, LA 70803, USA.
Abstract:
Cytokine-activated macrophages (MPhi) employ reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) to combat pathogens. The requirement for ROI for an effective host response to experimental leprosy using mice which have a disruption in the 91-kD subunit of the NAPDH oxidase cytochrome b (phox91-/-) was examined. Mycobacterium leprae multiplication in phox91-/- foot pads (FP) was elevated early in infection but subsequently arrested similarly to control mice within a noninvasive granuloma. Using a modified lepromin test model, a similar cellular composition in the M. leprae-induced FP granuloma in both strains with lymphocyte infiltration consisting primarily of CD4+CD44(hi)CD62L(lo) effector cells was found. Of great interest was the disparity in the T cell population between the granuloma and the draining lymph node which contained predominantly naïve CD4+CD44(lo)CD62L(hi) cells and was, therefore, not representative of the infection site. TH1 cytokines, chemokines and inducible nitric oxide synthase were comparably expressed in the FP of both strains. When infected in vitro, normal MPhi from B6 and phox91-/- mice supported bacterial viability, whereas IFNgamma-activated MPhi killed M. leprae in a RNI-dependent manner, emphasizing that ROI was dispensable. These data show that phox91-/- mice generate a strong adaptive immune response and control long-term infection with M. leprae.
Insights
Mice lacking reactive oxygen intermediates (ROI) controlled leprosy infection, demonstrating that reactive nitrogen intermediates (RNI) are crucial for host defense against Mycobacterium leprae.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis of infectious diseases
Background:
- Macrophages (MPhi) use reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) to fight pathogens.
- Leprosy is caused by Mycobacterium leprae, and the host immune response is critical for control.
Purpose of the Study:
- To investigate the role of ROI in host defense against experimental leprosy.
- To determine if ROI are essential for controlling Mycobacterium leprae infection.
Main Methods:
- Used phox91-/- mice, which have a disruption in NADPH oxidase cytochrome b, lacking ROI production.
- Infected mice with Mycobacterium leprae and analyzed foot pad granulomas and draining lymph nodes.
- Assessed immune cell populations (CD4+, CD44, CD62L) and cytokine/chemokine expression.
- In vitro infection of macrophages with Mycobacterium leprae.
Main Results:
- phox91-/- mice controlled Mycobacterium leprae infection similarly to control mice, forming non-invasive granulomas.
- Granulomas in both strains had similar cellular composition, with effector T cells (CD4+CD44(hi)CD62L(lo)).
- In vitro, IFNgamma-activated macrophages killed M. leprae in a RNI-dependent manner, indicating ROI dispensability.
Conclusions:
- Reactive oxygen intermediates (ROI) are dispensable for controlling Mycobacterium leprae infection.
- Reactive nitrogen intermediates (RNI)-dependent mechanisms are sufficient for host defense against leprosy.
- Mice lacking ROI can mount a strong adaptive immune response and control long-term infection.
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