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Published on: July 16, 2019
Murine splenocytes produce inflammatory cytokines in a MyD88-dependent response to Bacillus anthracis spores
Ian J Glomski1, Jörg H Fritz, Selina J Keppler
1Institut Pasteur, Unité des Toxines et Pathogénie Bactérienne, Paris, F-75015, France.
Abstract:
Bacillus anthracis is a sporulating Gram-positive bacterium that causes the disease anthrax. The highly stable spore is the infectious form of the bacterium that first interacts with the prospective host, and thus the interaction between the host and spore is vital to the development of disease. We focused our study on the response of murine splenocytes to the B. anthracis spore by using paraformaldehyde-inactivated spores (FIS), a treatment that prevents germination and production of products associated with vegetative bacilli. We found that murine splenocytes produce IL-12 and IFN-gamma in response to FIS. The IL-12 was secreted by CD11b cells, which functioned to induce the production of IFN-gamma by CD49b (DX5) NK cells. The production of these cytokines by splenocytes was not dependent on TLR2, TLR4, TLR9, Nod1, or Nod2; however, it was dependent on the signalling adapter protein MyD88. Unlike splenocytes, Nod1- and Nod2-transfected HEK cells were activated by FIS. Both IL-12 and IFN-gamma secretion were inhibited by treatment with B. anthracis lethal toxin. These observations suggest that the innate immune system recognizes spores with a MyD88-dependent receptor (or receptors) and responds by secreting inflammatory cytokines, which may ultimately aid in resisting infection.
Insights
The innate immune system recognizes Bacillus anthracis spores via a MyD88-dependent pathway, triggering the release of IL-12 and IFN-gamma. This response, crucial for fighting anthrax infection, involves specific immune cells and is modulated by bacterial toxins.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Bacillus anthracis spores are the infectious form of anthrax, initiating host interaction.
- Understanding host-pathogen interactions is vital for disease development and immune response.
- The innate immune system's recognition of bacterial spores is a key factor in controlling infection.
Purpose of the Study:
- To investigate the murine splenocyte response to inactivated Bacillus anthracis spores.
- To identify the immune pathways and cellular players involved in spore recognition.
- To determine the role of specific pattern recognition receptors and signaling molecules.
Main Methods:
- Utilized paraformaldehyde-inactivated spores (FIS) to study B. anthracis spore-host interactions.
- Analyzed cytokine production (IL-12, IFN-gamma) by murine splenocytes.
- Investigated the involvement of Toll-like receptors (TLR2, TLR4, TLR9), Nod1, Nod2, and MyD88.
- Examined responses in transfected HEK cells and the effect of B. anthracis lethal toxin.
Main Results:
- Murine splenocytes produced IL-12 and IFN-gamma in response to FIS.
- IL-12 was secreted by CD11b cells, inducing IFN-gamma production by NK cells (CD49b/DX5).
- Cytokine production was MyD88-dependent but independent of TLR2, TLR4, TLR9, Nod1, or Nod2; however, Nod1 and Nod2 activated HEK cells.
- B. anthracis lethal toxin inhibited IL-12 and IFN-gamma secretion.
Conclusions:
- The innate immune system recognizes B. anthracis spores through a MyD88-dependent mechanism.
- This recognition leads to the secretion of inflammatory cytokines, potentially aiding in infection resistance.
- Specific immune cells and signaling pathways are critical for the host response to anthrax spores.
