Suppression of Fcγ-receptor-mediated antibody effector function during persistent viral infection.

TitleSuppression of Fcγ-receptor-mediated antibody effector function during persistent viral infection.
Publication TypeJournal Article
Year of Publication2015
AuthorsYamada DH, Elsaesser H, Lux A, Timmerman JM, Morrison SL, de la Torre JCarlos, Nimmerjahn F, Brooks DG
JournalImmunity
Volume42
Issue2
Pagination379-90
Date Published2015 Feb 17
ISSN1097-4180
Abstract

Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. Herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (LCMV) suppressed multiple Fcγ-receptor (FcγR) functions. The high amounts of immune complexes suppressed antibody-mediated cell depletion, therapeutic antibody-killing of LCMV infected cells and human CD20-expressing tumors, as well as reduced immune complex-mediated cross-presentation to T cells. Suppression of FcγR activity was not due to inhibitory FcγRs or high concentrations of free antibody, and proper FcγR functions were restored when persistently infected mice specifically lacked immune complexes. Thus, we identify a mechanism of immunosuppression during viral persistence with implications for understanding effective antibody activity aimed at pathogen control.

DOI10.1016/j.immuni.2015.01.005
Alternate JournalImmunity
PubMed ID25680277
PubMed Central IDPMC4334737
Grant ListAI082975 / AI / NIAID NIH HHS / United States
AI085043 / AI / NIAID NIH HHS / United States
AI109627 / AI / NIAID NIH HHS / United States
P30 AI028697 / AI / NIAID NIH HHS / United States
R01 AI085043 / AI / NIAID NIH HHS / United States
R01 CA162964 / CA / NCI NIH HHS / United States
R21 AI077012 / AI / NIAID NIH HHS / United States
R21 AI109627 / AI / NIAID NIH HHS / United States
U01 AI082975 / AI / NIAID NIH HHS / United States
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