Streptococcus pneumoniae (Spn) colonizes the nasopharynx and can cause pneumonia. From the lungs it spreads to the bloodstream and causes organ damage. We characterized the in vivo Spn and mouse transcriptomes within the nasopharynx, lungs, blood, heart, and kidneys using three Spn strains. We identified Spn genes highly expressed at all anatomical sites and in an organ-specific manner; highly expressed genes were shown to have vital roles with knockout mutants. The in vivo bacterial transcriptome during colonization/disease was distinct from previously reported in vitro transcriptomes. Distinct Spn and host gene-expression profiles were observed during colonization and disease states, revealing specific genes/operons whereby Spn adapts to and influences host sites in vivo. We identified and experimentally verified host-defense pathways induced by Spn during invasive disease, including proinflammatory responses and the interferon response. These results shed light on the pathogenesis of Spn and identify therapeutic targets.

Macrophages are a specialized class of innate immune cells with multifaceted roles in modulation of the inflammatory response, homeostasis, and wound healing. While developmentally derived or originating from circulating monocytes, naïve macrophages can adopt a spectrum of context-dependent activation states ranging from pro-inflammatory (classically activated, M1) to pro-wound healing (alternatively activated, M2). Tumors are known to exploit macrophage polarization states to foster a tumor-permissive milieu, particularly by skewing macrophages toward a pro-tumor (M2) phenotype. These pro-tumoral macrophages can support cancer progression by several mechanisms including immune suppression, growth factor production, promotion of angiogenesis and tissue remodeling. By preventing the adoption of this pro-tumor phenotype or reprogramming these macrophages to a more pro-inflammatory state, it may be possible to inhibit tumor growth. Here, we describe types of tumor-derived signaling that facilitate macrophage reprogramming, including paracrine signaling and activation of innate immune checkpoints. We also describe intervention strategies targeting macrophage plasticity to limit disease progression and address their implications in cancer chemo- and immunotherapy.

To better prepare physiology students for 21st century careers, we incorporated classroom-based undergraduate research experiences and service learning/community-engaged learning (SLCE) into a college-level physiology laboratory course. The interventions were incorporated over 4 yr and assessed using validated surveys of student-reported learning gains related to attitudes toward science, the scientific process, and career paths. Students reported the greatest learning gains in those years when students did novel research oriented around a common theme of water quality. The gains were greater than those of a matched cohort that participated in an apprentice-style summer undergraduate research experience. With respect to the SLCE related to youth science literacy, students provided evidence of learning related to academics, personal growth, and civic mindedness. For example, many expressed discomfort about being in a new situation, often describing the differences between themselves and the youth with whom they interacted. However, students also grew in confidence about collaborating with people who were different from them and in their role as the “scientist.” Limitations of the study include the quasi-experimental design and the incorporation of multiple interventions at the same time. Future studies should examine improvement in content acquisition and competency-based learning skills. Nonetheless, these results suggest that both novel research and SLCE increase student learning in the context of an undergraduate physiology laboratory course. Many of the learning gains observed with the SLCE are particularly important for physiology students, many of whom aspire to careers in health sciences, where they will be regularly working with nonscientists.