TY - JOUR
T1 - IL-27 receptor signaling regulates memory CD4+ t cell populations and suppresses rapid inflammatory responses during secondary malaria infection
AU - Findlay, Emily Gwyer
AU - Villegas-Mendez, Ana
AU - O'Regan, Noelle
AU - Brian de Souza, J.
AU - Grady, Lisa Marie
AU - Saris, Christiaan J.
AU - Riley, Eleanor M.
AU - Couper, Kevin N.
PY - 2014/1
Y1 - 2014/1
N2 - Interleukin-27 (IL-27) is known to control primary CD4+ T cell responses during a variety of different infections, but its role in regulating memory CD4+ T responses has not been investigated in any model. In this study, we have examined the functional importance of IL-27 receptor (IL-27R) signaling in regulating the formation and maintenance of memory CD4+ T cells following malaria infection and in controlling their subsequent reactivation during secondary parasite challenge. We demonstrate that although the primary effector/memory CD4+ T cell response was greater in IL-27R-deficient (WSX-1-/-) mice following Plasmodium berghei NK65 infection than in wild-type (WT) mice, there were no significant differences in the size of the maintained memory CD4+ T population(s) at 20 weeks postinfection in the spleen, liver, or bone marrow of WSX-1-/- mice compared with WT mice. However, the composition of the memory CD4+ T cell pool was slightly altered in WSX-1-/- mice following clearance of primary malaria infection, with elevated numbers of late effector memory CD4+ T cells in the spleen and liver and increased production of IL-2 in the spleen. Crucially, WSX-1-/- mice displayed significantly enhanced parasite control compared with WT mice following rechallenge with homologous malaria parasites. Improved parasite control in WSX-1-/- mice during secondary infection was associated with elevated systemic production of multiple inflammatory innate and adaptive cytokines and extremely rapid proliferation of antigen-experienced T cells in the liver. These data are the first to demonstrate that IL-27R signaling plays a role in regulating the magnitude and quality of secondary immune responses during rechallenge infections. © 2014, American Society for Microbiology.
AB - Interleukin-27 (IL-27) is known to control primary CD4+ T cell responses during a variety of different infections, but its role in regulating memory CD4+ T responses has not been investigated in any model. In this study, we have examined the functional importance of IL-27 receptor (IL-27R) signaling in regulating the formation and maintenance of memory CD4+ T cells following malaria infection and in controlling their subsequent reactivation during secondary parasite challenge. We demonstrate that although the primary effector/memory CD4+ T cell response was greater in IL-27R-deficient (WSX-1-/-) mice following Plasmodium berghei NK65 infection than in wild-type (WT) mice, there were no significant differences in the size of the maintained memory CD4+ T population(s) at 20 weeks postinfection in the spleen, liver, or bone marrow of WSX-1-/- mice compared with WT mice. However, the composition of the memory CD4+ T cell pool was slightly altered in WSX-1-/- mice following clearance of primary malaria infection, with elevated numbers of late effector memory CD4+ T cells in the spleen and liver and increased production of IL-2 in the spleen. Crucially, WSX-1-/- mice displayed significantly enhanced parasite control compared with WT mice following rechallenge with homologous malaria parasites. Improved parasite control in WSX-1-/- mice during secondary infection was associated with elevated systemic production of multiple inflammatory innate and adaptive cytokines and extremely rapid proliferation of antigen-experienced T cells in the liver. These data are the first to demonstrate that IL-27R signaling plays a role in regulating the magnitude and quality of secondary immune responses during rechallenge infections. © 2014, American Society for Microbiology.
U2 - 10.1128/IAI.01091-13
DO - 10.1128/IAI.01091-13
M3 - Article
C2 - 24101691
SN - 1098-5522
VL - 82
SP - 10
EP - 20
JO - Infection and immunity
JF - Infection and immunity
IS - 1
ER -