Endogenous interleukin-10 is required for prevention of a hyperinflammatory intracerebral immune response in Listeria monocytogenes meningoencephalitis.
To analyze the role of interleukin-10 (IL-10) in bacterial cerebral infections, we studied cerebral listeriosis in IL-10-deficient (IL-10(-/-)) and wild-type (WT) mice, the latter of which express high levels of IL-10 in both primary and secondary cerebral listeriosis. IL-10(-/-) mice succumbed to primary as well as secondary listeriosis, whereas WT mice were significantly protected from secondary listeriosis by prior intraperitoneal immunization with Listeria monocytogenes. Meningoencephalitis developed in both strains; however, in IL-10(-/-) mice the inflammation was more severe and associated with increased brain edema and multiple intracerebral hemorrhages. IL-10(-/-) mice recruited significantly increased numbers of leukocytes, in particular granulocytes, to the brain, and the intracerebral cytokine (tumor necrosis factor, IL-1, IL-12, gamma interferon, and inducible nitric oxide synthase) and chemokine (crg2/IP-10, RANTES, MuMig, macrophage inflammatory protein 1alpha [MIP-1alpha], and MIP-1beta) transcription was enhanced compared to that in WT mice. Despite this prominent hyperinflammation, the frequencies of intracerebral L. monocytogenes-specific CD8(+) T cells were reduced and the intracerebral bacterial load was not reduced in IL-10(-/-) mice compared to WT mice. Following intraperitoneal infection, IL-10(-/-) mice exhibited hepatic hyperinflammation without better bacterial clearance; however, in contrast to the mice with cerebral listeriosis, they did not succumb, illustrating that intrinsic factors of the target organ have a strong impact on the course and outcome of the infection.
Deckert
M
M
Institut für Neuropathologie, Universitätsklinken Bonn, Bonn, Germany.
Soltek
S
S
Geginat
G
G
Lütjen
S
S
Montesinos-Rongen
M
M
Hof
H
H
Schlüter
D
D
D000818:Animals; D001929:Brain Edema / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D020299:Intracranial Hemorrhage, Hypertensive / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008590:Meningoencephalitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger
D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10