Resolution of a chronic viral infection after interleukin-10 receptor blockade

By Mette Ejrnaes, Christophe M. Filippi, M. Martinic, E. Ling, Lisa Togher, Shane Crotty, M. von Herrath. Journal of Experimental Medicine, 2006

1,011 citations recorded by the source corpus.

A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function of T cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon γ production by antiviral CD8+ T cells was enhanced. In persistently infected mice, CD8α+ dendritic cell (DC) numbers declined early after infection, whereas CD8α− DC numbers were not affected. CD8α− DCs supported IL-10 production and subsequent dampening of antiviral T cell responses. Therapeutic IL-10R blockade broke the cycle of IL-10–mediated immune suppression, preventing IL-10 priming by CD8α− DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/41bf05986cd4b2ed17ea17298848fcf8e8c13710

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Citations in the corpus

Viral evasion and subversion of pattern-recognition receptor signalling (2008, background): “Another potential effect of viral manipulation of TLRs involves the selective stimulation of TLR pathways that lead to the production of IL-10, a cytokine that is required for viral persistence 104, 105 .”
The regulation of IL-10 production by immune cells (2010, background): “Although the absence of IL-10 leads to better clearance of some pathogens with no enhanced immunopatholog”
Shaping and reshaping CD8+ T-cell memory (2008, background): “In addition, other recent studies suggest that IL-10 production during chronic infection limits memory CD8 + T-cell antiviral activit”
T cell exhaustion (2011, background): “Moreover, IL-10 is linked to T cell dysfunction during persistent viral infection, as blockade of IL-10 enhances viral control and improves T cell response”
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. (2019, background): “During chronic LCMV infection, blocking IL-10 in combination with PD-1 results in the maintenance of robust Teff responses, development of functional antiviral memory cells, and faster control of viral replication (143, 144, 151).”
Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus Infections (2009, background): “The late-peaking IL-10 response may not only be too late to subdue immunopathogenic levels of proinflammatory cytokine production but may also contribute to HIV persistence by driving the exhaustion of virus-specific CD8 T cells (8, 15).”
TH1 cells control themselves by producing interleukin-10 (2007, background): “More recently, the production of IL-10 was shown to maintain a chronic non-healing lymphocytic choriomeningitis virus infection, and the neutralization of IL-10 resulted in the clearance of this viru”
Redefining chronic viral infection. (2009, positive): “For example, when the IL-10 pathway was blocked, virus-specific CD8 T cell responses to chronic infection with LCMV were enhanced (Ejrnaes et al., 2006; Brooks et al., 2006).”
Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10 (2009, background): “More recently, IL-10 has been found to mediate virus persistence during chronic viral infection”
Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) (2020, neutral): “Importantly, blocking IL-10 function has been shown to successfully prevent T cell exhaustion in animal models of chronic infection (35, 36).”
IL-10: The Master Regulator of Immunity to Infection (2008, background): “(31), and lymphocytic choriomeningitis virus (32, 33) to the extent that pathogens escape immune control, resulting in either fulminant and rapidly fatal or chronic nonhealing infections.”