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

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

New developments in the analysis of catch time series as the basis for fish stock assessments: The CMSY++ method

Following an introduction to the nature of fisheries catches and their information content, a new development of CMSY, a data-limited stock assessment method for fishes and invertebrates, is presented. This new version, CMSY++, overcomes several of the deficiencies of CMSY, which itself improved upon the “Catch-MSY” method published by S. Martell and R. Froese in 2013. The catch-only application of CMSY++ uses a Bayesian implementation of a modified Schaefer model, which also allows the fitting of abundance indices should such information be available. In the absence of historical catch time series and abundance indices, CMSY++ depends strongly on the provision of appropriate and informative priors for plausible ranges of initial and final stock depletion. An Artificial Neural Network (ANN) now assists in selecting objective priors for relative stock size based on patterns in 400 catch time series used for training. Regarding the cross-validation of the ANN predictions, of the 400 real stocks used in the training of ANN, 94% of final relative biomass (B/k) Bayesian (BSM) estimates were within the approximate 95% confidence limits of the respective CMSY++ estimate. Also, the equilibrium catch-biomass relations of the modified Schaefer model are compared with those of alternative surplus-production and age-structured models, suggesting that the latter two can be strongly biased towards underestimating the biomass required to sustain catches at low abundance. Numerous independent applications demonstrate how CMSY++ can incorporate, in addition to the required catch time series, both abundance data and a wide variety of ancillary information. We stress, however, the caveats and pitfalls of naively using the built-in prior options, which should instead be evaluated case-by-case and ideally be replaced by independent prior knowledge

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

A genetic absence of the common IFN- α/β signaling receptor (IFNAR) in mice is associated with enhanced viral replication and altered adaptive immune responses. However, analysis of IFNAR-/- mice is limited for studying the functions of type I IFN at discrete stages of viral infection. To define the temporal functions of type I IFN signaling in the context of infection by West Nile virus (WNV), we treated mice with MAR1-5A3, a neutralizing, non cell-depleting anti-IFNAR antibody. Inhibition of type I IFN signaling at or before day 2 after infection was associated with markedly enhanced viral burden, whereas treatment at day 4 had substantially less effect on WNV dissemination. While antibody treatment prior to infection resulted in massive expansion of virus-specific CD8+ T cells, blockade of type I IFN signaling starting at day 4 induced dysfunctional CD8+ T cells with depressed cytokine responses and expression of phenotypic markers suggesting exhaustion. Thus, only the later maturation phase of anti-WNV CD8+ T cell development requires type I IFN signaling. WNV infection experiments in BATF3-/- mice, which lack CD8-α dendritic cells and have impaired priming due to inefficient antigen cross-presentation, revealed a similar effect of blocking IFN signaling on CD8+ T cell maturation. Collectively, our results suggest that cell non-autonomous type I IFN signaling shapes maturation of antiviral CD8+ T cell response at a stage distinct from the initial priming event