In:
The Journal of Immunology, The American Association of Immunologists, Vol. 198, No. 1_Supplement ( 2017-05-01), p. 78.24-78.24
Abstract:
Herpesviruses have co-evolved with their hosts for million of years, establishing an intimate balancing act of lifelong infection with minimal damage to the host. Interleukin (IL)-10 is a major inhibitory cytokine that has been usurped by many herpesviruses to facilitate infection. Here we tested the consequence of IL-10 deficiency on the outcome of murine gammaherpesvirus 68 (γHV68) infection, a small animal model of γHV pathogenesis. While IL-10 deficiency had minimal impact on the control of virus infection, IL-10 deficient mice showed hyper-activation of the immune response with increased levels of T cell activation, effector T cells and prolonged neutrophilia in the infected lung. IL-10 further had a non-redundant role in limiting intestinal inflammation with chronically infected mice showing a prolonged failure to thrive following infection, associated with enhanced colonic Th1 responses. CD4 T cells were a prominent source of IL10 during acute and chronic infection, with IL10+ interferon-gamma+ FoxP3- type 1 regulatory CD4 T cells as the major early source of IL10. High-dimensional mass cytometric analysis of IL10 expressing cells, and IL10 responsive cells, identified a constellation of phenotypes that correlate with robust IL10 expression, and further identified direct and indirect targets of IL10. In total, these data demonstrate the context dependent role of IL10 in constraining the antiviral host response and identify IL10-dependent and –independent regulatory pathways in regulating chronic herpesvirus infection. This research was funded by grants from the American Heart Association, Crohn’s and Colitis Foundation of America and the UC Department of Anesthesiology (ETC).
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.198.Supp.78.24
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2017
detail.hit.zdb_id:
1475085-5
