Interplay between T Regulatory and T Helper 17 Lymphocytes in Modulation of Immunity to Blood Stage Malaria Infection

Malaria claims millions of lives worldwide each year. While a pro-inflammatory immune response is required to control parasite replication and promote clearance of infected erythrocytes, considerable disease pathology is caused by an excessive and dysregulated inflammatory reactivity to blood stage infection. Clinical symptoms, including fever and chills, correspond to production by CD4+ T helper (Th) lymphocytes of high levels of pro-inflammatory cytokines including tumour necrosis factor-α, interleukin-12 and interferon- γ in response to parasite components released upon erythrocyte rupture. Differentiation into specific effector Th subsets is directed by polarizing cytokines and expression of master transcription factors. From a perspective of homeostasis, further regulatory Th subsets have been described that secrete specific cytokines to modulate the effector immune response and thus play a pivotal role in protecting the body from direct and indirect pathogenic effects of malaria infection. In particular, T regulatory (Treg) lymphocytes are associated with immune tolerance and play a crucial role in suppressing the host response by inhibiting the function of effector subsets such as Th1 and Th17. This prevents inflammation produced downstream by (non-T) effectors cells. Treg lymphocytes, exemplified by CD4+CD25+Foxp3+ cells, gradually increase in number during infection to achieve and maintain the homeostasis of an otherwise imbalanced T cell response. This editorial discusses the production of Treg and Th17 lymphocytes and the interrelated roles played by their signature cytokines during malaria infection and considers the contribution of each to parasite clearance or progression

MUFFINN: cancer gene discovery via network analysis of somatic mutation data

A major challenge for distinguishing cancer-causing driver mutations from inconsequential passenger mutations is the long-tail of infrequently mutated genes in cancer genomes. Here, we present and evaluate a method for prioritizing cancer genes accounting not only for mutations in individual genes but also in their neighbors in functional networks, MUFFINN (MUtations For Functional Impact on Network Neighbors). This pathway-centric method shows high sensitivity compared with gene-centric analyses of mutation data. Notably, only a marginal decrease in performance is observed when using 10 % of TCGA patient samples, suggesting the method may potentiate cancer genome projects with small patient populations.This research was partly supported by grants from the National Research Foundation of Korea (2012M3A9B4028641, 2012M3A9C7050151, 2015R1A2A1A15055859), Brain Korea 21 (BK21) PLUS program to I.L., Global PH.D Fellowship Program through the National Research Foundation of Korea (2011-0008548) to A.C., the European Research Council (Consolidator grant IR-DC, 616434), the Spanish Ministry of Economy and Competitiveness (BFU2011-26206 and SEV-2012-0208), the AXA Research Fund, and AGAUR to B.L., the FP7 FET grant MAESTRA (ICT-2013-612944) and Marie Curie Actions to F.S