Abstract
Whilst mast cells participate in the immune defence against the intracellular bacterium Listeria monocytogenes, there is conflicting evidence regarding the ability of L. monocytogenes to infect mast cells. It is known that the pore-forming toxin listeriolysin (LLO) is important for mast cell activation, degranulation and the release of pro-inflammatory cytokines. Mast cells, however, are a potential source of a wide range of cytokines, chemokines and other mediators including osteopontin, which contributes to the clearing of L. monocytogenes infections in vivo, although its source is unknown. We therefore aimed to resolve the controversy of mast cell infection by L. monocytogenes and investigated the extent of mediator release in response to the bacterium. In this paper we show that the infection of bone marrow-derived mast cells by L. monocytogenes is inefficient and LLO-independent. LLO, however, is required for calcium-independent mast cell degranulation as well as for the transient and selective downregulation of cell surface CD117 (c-kit) on mast cells. We demonstrate that in addition to the key pro-inflammatory cytokines TNF-α and IL-6, mast cells release a wide range of other mediators in response to L. monocytogenes. Osteopontin, IL-2, IL-4, IL-13 and granulocyte macrophage colony-stimulating factor (GM-CSF), and chemokines including CCL2, CCL3, CCL4 and CCL5 are released in a MyD88-dependent manner. The wide range of mediators released by mast cells in response to L. monocytogenes may play an important role in the recruitment and activation of a variety of immune cells in vivo. The cocktail of mediators, however, is unlikely to skew the immune response to a particular effector response. We propose that mast cells provide a hitherto unreported source of osteopontin, and may provide an important role in co-ordinating the immune response during Listeria infection.
Highlights
Mast cells are traditionally associated with the immune response against multi-cellular parasites and the pathogenesis of allergy and asthma, there is increasing evidence that they are important in immunity to pathogenic bacteria [1]
In an effort to resolve the controversy regarding the ability of L. monocytogenes to infect mast cells, we examined the infection of bone marrow-derived mast cells (BMMC) using two independent assays
One major limitation of the mouse model for L. monocytogenes infection is that the bacterial internalin A (InlA) cannot bind to mouse E-cadherin [18]
Summary
Mast cells are traditionally associated with the immune response against multi-cellular parasites and the pathogenesis of allergy and asthma, there is increasing evidence that they are important in immunity to pathogenic bacteria [1]. They are strategically located at the interface between the host and the environment, including the gut, allowing direct interaction with bacteria and bacterial products [1,2]. TNF-a, is just one of the cytokines released in response to L. monocytogenes with other pro-inflammatory cytokines, including IL-6 and IL-1b, released during infection in vivo [7,8], and mast cells have been shown to secrete these in response to L. monocytogenes in vitro [7,9,10]
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