Host Resistance to Plasmodium-Induced Acute Immune Pathology Is Regulated by Interleukin-10 Receptor Signaling.

Carla Claser; J Brian De Souza; Samuel G Thorburn; Georges Emile Grau; Eleanor M Riley; Laurent Rénia; Julius CR Hafalla ORCID logo; (2017) Host Resistance to Plasmodium-Induced Acute Immune Pathology Is Regulated by Interleukin-10 Receptor Signaling. Infection and immunity, 85 (6). e00941-e00916. ISSN 0019-9567 DOI: 10.1128/IAI.00941-16
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The resolution of malaria infection is dependent on a balance between proinflammatory and regulatory immune responses. While early effector T cell responses are required for limiting parasitemia, these responses need to be switched off by regulatory mechanisms in a timely manner to avoid immune-mediated tissue damage. Interleukin-10 receptor (IL-10R) signaling is considered to be a vital component of regulatory responses, although its role in host resistance to severe immune pathology during acute malaria infections is not fully understood. In this study, we have determined the contribution of IL-10R signaling to the regulation of immune responses during Plasmodium berghei ANKA-induced experimental cerebral malaria (ECM). We show that antibody-mediated blockade of the IL-10R during P. berghei ANKA infection in ECM-resistant BALB/c mice leads to amplified T cell activation, higher serum gamma interferon (IFN-γ) concentrations, enhanced intravascular accumulation of both parasitized red blood cells and CD8+ T cells to the brain, and an increased incidence of ECM. Importantly, the pathogenic effects of IL-10R blockade during P. berghei ANKA infection were reversible by depletion of T cells and neutralization of IFN-γ. Our findings underscore the importance of IL-10R signaling in preventing T-cell- and cytokine-mediated pathology during potentially lethal malaria infections.


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