Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria.
Balanced induction of proinflammatory and type I IFN responses upon activation of Toll-like receptors (TLRs) determines the outcome of microbial infections and the pathogenesis of autoimmune and other inflammatory diseases. Mast cells, key components of the innate immune system, are known for their debilitating role in allergy and autoimmunity. However, their role in antimicrobial host defenses is being acknowledged increasingly. How mast cells interact with microbes and the nature of responses triggered thereby is not well characterized. Here we show that in response to TLR activation by Gram-positive and -negative bacteria or their components, mast cells elicit proinflammatory but not type I IFN responses. We demonstrate that in mast cells, bound bacteria and TLR ligands remain trapped at the cell surface and do not undergo internalization, a prerequisite for type I IFN induction. Such cells, however, can elicit type I IFNs in response to vesicular stomatitis virus which accesses the cytosolic retinoic acid-inducible gene I receptor. Although important for antiviral immunity, a strong I IFN response is known to contribute to pathogenesis of several bacterial pathogens such as Listeria monocytogenes. Interestingly, we observed that the mast cell-dependent neutrophil mobilization upon L. monocytogenes infection is highly impaired by IFN-beta. Thus, the fact that mast cells, although endowed with the capacity to elicit type I IFNs in response to viral infection, elicit only proinflammatory responses upon bacterial infection shows that mast cells, key effector cells of the innate immune system, are well adjusted for optimal antibacterial and antiviral responses.
Dietrich
Nicole
N
Department of Molecular Immunology, Helmholtz-Centre for Infection Research, 38124 Braunschweig, Germany.
Rohde
Manfred
M
Geffers
Robert
R
Kröger
Andrea
A
Hauser
Hansjörg
H
Weiss
Siegfried
S
Gekara
Nelson O
NO
D000143:Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology* / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects; D018116:Vesiculovirus / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure
D000143:Acids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D016899:Interferon-beta