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Dissociation of innate immune responses in microglia infected with Listeria monocytogenes
Author(s) -
FrandeCabanes Elisabet,
FernandezPrieto Lorena,
CalderonGonzalez Ricardo,
RodríguezDel Río Estela,
YañezDiaz Sonsoles,
LópezFanarraga Monica,
AlvarezDomínguez Carmen
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22602
Subject(s) - microglia , biology , innate immune system , phagosome , immune system , chemokine , tumor necrosis factor alpha , neuroinflammation , microbiology and biotechnology , listeria infection , immunology , listeria monocytogenes , inflammation , listeria , phagocytosis , bacteria , genetics
Microglia, the innate immune cells of the brain, plays a central role in cerebral listeriosis. Here, we present evidence that microglia control Listeria infection differently than macrophages. Infection of primary microglial cultures and murine cell lines with Listeria resulted in a dual function of the two gene expression programmes involved in early and late immune responses in macrophages. Whereas the bacterial gene hly seems responsible for both transcriptional programmes in macrophages, Listeria induces in microglia only the tumor necrosis factor (TNF)‐regulated transcriptional programme. Listeria also represses in microglia the late immune response gathered in two clusters, microbial degradation, and interferon (IFN)‐inducible genes. The bacterial gene actA was required in microglia to induce TNF‐regulated responses and to repress the late response. Isolation of microglial phagosomes revealed a phagosomal environment unable to destroy Listeria . Microglial phagosomes were also defective in several signaling and trafficking components reported as relevant for Listeria innate immune responses. This transcriptional strategy in microglia induced high levels of TNF‐α and monocyte chemotactic protein‐1 and low production of other neurotoxic compounds such as nitric oxide, hydrogen peroxide, and Type I IFNs. These cytokines and toxic microglial products are also released by primary microglia, and this cytokine and chemokine cocktail display a low potential to trigger neuronal apoptosis. This overall bacterial strategy strongly suggests that microglia limit Listeria inflammation pattern exclusively through TNF‐mediated responses to preserve brain integrity. GLIA 2014;62:233–246