IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

• DOI: 10.1371/journal.ppat.1005999
• Publication Date: 2016-11-03T17:41:30Z
• Authors: Ismail Sebina; Kylie R. James; Megan S. F. Soon; Lily G. Fogg; Shannon E. Best; Fabian de Labasti...; Marcela Montes de...; Fiona H. Amante; Bryce S. Thomas; Lynette Beattie; Fernando Souza-Fo...; Mark J. Smyth; Paul J. Hertzog; Geoffrey R. Hill; Andreas Hutloff; Christian R. Engw...; Ashraful Haque
• Keywords: Plasmodium chabaudi; Plasmodium yoelii; Humoral immunity

Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations this have focused on antigenic variation by Plasmodium, but considered less whether host production of parasite-specific antibody is sub-optimal. In particular, unclear immune factors might limit responses. Here, we explored the effect Type I Interferon signalling via IFNAR1 CD4+ T-cell and B-cell responses two non-lethal murine models malaria, P. chabaudi AS (PcAS) yoelii 17XNL (Py17XNL) Firstly, demonstrated that T-cells ICOS-signalling were crucial generating germinal centre (GC) B-cells, plasmablasts antibodies, likewise T follicular helper (Tfh) cell relied B cells. Next, found IFNAR1-signalling impeded resolution infection, which was associated with impaired IgM several IgG sub-classes. Consistent this, GC formation, Ig-class switching, plasmablast Tfh differentiation all IFNAR1-signalling. proceeded conventional dendritic cells, acted early limiting activation, proliferation ICOS expression T-cells, restricting localization activated adjacent within areas spleen, simultaneously suppressing Th1 Finally, IFNAR1-deficiency accelerated parasite control boosting ICOS-signalling. Thus, provide evidence a innate cytokine response impedes onset immunity during experimental malaria.