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The cellular source of interleukin-6 during Listeria infection
1Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Abstract:
The cellular source of interleukin-6 (IL-6) during infection of mice with Listeria monocytogenes was investigated both in vitro and in vivo. Peritoneal cells taken at intervals from infected mice and cultured in vitro without added stimulus produced high titers of IL-6 peaking 2 days postinfection in a time course similar to that observed in vivo. Adherent cells with the morphology of macrophages were a major source of this IL-6. Spleen cells similarly harvested at intervals and cultured with heat-killed Listeria or heat-killed Brucella organisms as specific and nonspecific stimuli, respectively, showed two distinct IL-6 responses: (i) an early-phase response up to 5 days after infection when IL-6 production was elicited by either a specific or nonspecific stimulus, and when depletion of T cells had no effect, and (ii) a later response 7 to 10 days after infection when very high levels of IL-6 were produced in response to a specific stimulus. This response was lost when T cells were depleted in vitro or in vivo or in spleen cell cultures from mice with severe combined immunodeficiency. However, studies in vivo failed to show an important role for T cells governing serum IL-6. We conclude that most of IL-6 detected in vivo is produced by nonlymphocytes. Whether IL-6 produced by T lymphocytes in local foci of infection has any role in resolution of that infection is unknown.
Insights
Macrophages are the primary source of interleukin-6 (IL-6) during Listeria monocytogenes infection. While T cells influence later IL-6 responses, non-lymphocytes produce most IL-6 in vivo.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Interleukin-6 (IL-6) is a key cytokine in immune responses.
- Understanding the cellular sources of IL-6 is crucial for deciphering host defense mechanisms during infection.
Purpose of the Study:
- To identify the specific cell types responsible for producing IL-6 during Listeria monocytogenes infection in mice.
- To differentiate between early and late phase IL-6 production and the involvement of T cells.
Main Methods:
- In vitro and in vivo experiments using infected mice.
- Culture of peritoneal and spleen cells with various stimuli (heat-killed Listeria, heat-killed Brucella).
- T cell depletion studies and analysis of cells from mice with severe combined immunodeficiency.
Main Results:
- Peritoneal macrophages were identified as a major source of IL-6 early in infection.
- Spleen cells showed distinct early (T cell-independent) and late (T cell-dependent) IL-6 responses.
- In vivo studies indicated T cells do not significantly govern serum IL-6 levels.
- Most detected IL-6 in vivo originates from non-lymphoid cells.
Conclusions:
- Macrophages are a primary cellular source of IL-6 during Listeria infection.
- While T cells modulate later IL-6 responses, non-lymphocytes are the main producers of IL-6 in vivo.
- The role of T cell-derived IL-6 in local infection sites remains undetermined.