Fig. 7
PI3Kδ signaling regulates B cell specific IL-10 production in the lung following S. pneumoniae infection. a 24 h post S. pneumoniae infection, lung and spleen CFU counts were similar in wild-type, p110δE1020K-GL and p110δD910A mice. b 24 h post-infection, cytokine levels in the lung homogenate showed a trend towards increased TNFα, IL-6, and IL-1 in p110δE1020K mice. c 24 h prophylactic treatment with nemiralisib (nem) led to reduced levels of TNFα, IL-6, IL-1β, IFNγ, and IL-10 in the lungs of wild-type mice compared to vehicle control (veh) treated animals at 24 h post-infection. d Volcano plot (statistical significance against fold change) of the gene expression changes in response to nemiralisib treatment showed reduced levels of pro-inflammatory cytokines as well as IL-10 at 24 h post infection compared to vehicle control treatment. All genes analyzed are shown (gray dots) with the cytokines of interest labeled and colored; green for those with a negative fold change, red for positive fold change. e Analysis of immune cell subsets in Il10ITIB reporter mice at 24 h post-infection showed that the proportion of IL-10 producing B cells is significantly increased in p110δE1020K-GL mice and reduced in p110δD190A mice compared to wild-type mice, with similar trends in T cells and myeloid cells not reaching significance. (Mean values shown; data-points represent individual animals. a Results from two independent studies combined, n = 14; b representative data from three independent studies n = 8; c Combined data from four independent experiments n = 25; d data from 1 study, n = 6; e representative data from two independent studies n = 6)
