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 1α [MIP-1α], and MIP-1β) 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.