Modulation of natural killer activity in mice following infection with Listeria monocytogenes

Mice that received a sublethal, intraperitoneal dose of viable Listeria monocytogenes, virulent strain 10403, exhibited a systemic increase in natural killer (NK) activity. The kinetics of the response differed with respect to the various effector cell populations analyzed. Resident peritoneal cells and peripheral blood leukocytes demonstrated high NK activity on Days 3, 7, and 10. Peak spleen and bone marrow NK activity was observed on Day 3, returning to normal levels by Day 7. In contrast, peritoneal exudate cells, elicited with proteose peptone, expressed enhanced NK activity for 60 days following infection with viable Listeria. Augmented NK activity was detected with all cell types as early as 12 hr after infection. The intraperitoneal injection of nonviable antigenic preparations derived from L. monocytogenes, strain 10403, resulted in the enhancement of peritoneal and splenic NK activity. In contrast, mice that received an intraperitoneal injection of avirulent Listeria, strain 19113, failed to express enhanced levels of NK activity. The genetic trait of anti-listerial resistance which is associated with non-H-2 linked genes was of no importance with respect to enhanced NK activity. Listeria-resistant C57BL/6J and Listeria-susceptible DBA/2J mice both produced systemic augmentation of NK activity following infection. NK activity was not abrogated by macrophage depletion or by treatment with anti-Thy 1.2 serum plus complement. These results confirm the potent immunostimulatory capacity of virulent Listeria for NK activity and provide further insight into the kinetics of this response in various lymphoid compartments. The protracted augmentation of NK activity of elicited peritoneal exudate cells as compared to nonelicited peritoneal cells in Listeria-primed mice suggests that the influx of inflammatory cells may provide NK-enriched and/or accessory populations for immunopotentiation of NK activity in inflammatory sites.     

Sugar Industry Influence on the Scientific Agenda of the National Institute of Dental Research’s 1971 National Caries Program: A Historical Analysis of Internal Documents

Background

In 1966, the National Institute of Dental Research (NIDR) began planning a targeted research program to identify interventions for widespread application to eradicate dental caries (tooth decay) within a decade. In 1971, the NIDR launched the National Caries Program (NCP). The objective of this paper is to explore the sugar industry’s interaction with the NIDR to alter the research priorities of the NIDR NCP.

Methods and Findings

We used internal cane and beet sugar industry documents from 1959 to 1971 to analyze industry actions related to setting research priorities for the NCP. The sugar industry could not deny the role of sucrose in dental caries given the scientific evidence. They therefore adopted a strategy to deflect attention to public health interventions that would reduce the harms of sugar consumption rather than restricting intake. Industry tactics included the following: funding research in collaboration with allied food industries on enzymes to break up dental plaque and a vaccine against tooth decay with questionable potential for widespread application, cultivation of relationships with the NIDR leadership, consulting of members on an NIDR expert panel, and submission of a report to the NIDR that became the foundation of the first request for proposals issued for the NCP. Seventy-eight percent of the sugar industry submission was incorporated into the NIDR’s call for research applications. Research that could have been harmful to sugar industry interests was omitted from priorities identified at the launch of the NCP. Limitations are that this analysis relies on one source of sugar industry documents and that we could not interview key actors.

Conclusions

The NCP was a missed opportunity to develop a scientific understanding of how to restrict sugar consumption to prevent tooth decay. A key factor was the alignment of research agendas between the NIDR and the sugar industry. This historical example illustrates how industry protects itself from potentially damaging research, which can inform policy makers today. Industry opposition to current policy proposals—including a World Health Organization guideline on sugars proposed in 2014 and changes to the nutrition facts panel on packaged food in the US proposed in 2014 by the US Food and Drug Administration—should be carefully scrutinized to ensure that industry interests do not supersede public health goals.     

Vascular endothelial growth factor enhances macrophage clearance of apoptotic cells

Efficient clearance of apoptotic cells from the lung by alveolar macrophages is important for the maintenance of tissue structure and function. Lung tissue from humans with emphysema contains increased numbers of apoptotic cells and decreased levels of vascular endothelial growth factor (VEGF). Mice treated with VEGF receptor inhibitors have increased numbers of apoptotic cells and develop emphysema. We hypothesized that VEGF regulates apoptotic cell clearance by alveolar macrophages (AM) via its interaction with VEGF receptor 1 (VEGF R1). Our data show that the uptake of apoptotic cells by murine AMs and human monocyte-derived macrophages is inhibited by depletion of VEGF and that VEGF activates Rac1. Antibody blockade or pharmacological inhibition of VEGF R1 activity also decreased apoptotic cell uptake ex vivo. Conversely, overexpression of VEGF significantly enhanced apoptotic cell uptake by AMs in vivo. These results indicate that VEGF serves a positive regulatory role via its interaction with VEGF R1 to activate Rac1 and enhance AM apoptotic cell clearance.     

Inferring the phylogeography and evolutionary history of the splendid fairy-wren Malurus splendens from mitochondrial DNA and spectrophotometry

The phylogeographic structure of the widely distributed arid and semi-arid Australian splendid fairy-wren Malurus splendens was investigated by using variation in plumage characters and mitochondrial DNA (mtDNA). We examined sequences of the mtDNA ND2 gene and used spectrophotometry to quantify chromatic variation in plumage in order to test the current morphology-based intraspecific taxonomy of M. splendens and to discriminate between hypotheses invoking allopatric and parapatric processes in the origin of diversity in the complex. Genetic diversity of M. splendens fell into three divergent geographically structured clades. One represents populations ascribed to the western subspecies M. s. splendens , the other populations of central M. s. musgravi and the third all eastern populations currently ascribed to M. s. emmottorum and M. s. melanotus . Plumage patterns clearly differentiate M. s. splendens and M. s. musgravi, and spectrophotometry identified a step-wise transition in spectra between M. s. melanotus and M. s. emmottorum . Congruence of patterns of phenotypic and genetic variation among western, central and eastern populations of M. splendens strongly suggests that these populations have diverged in allopatry on either side of historical biogeographic barriers in this region. Decoupled patterns of phenotypic and genetic diversity suggest that the divergence of M. s. melanotus and M. s. emmottorum may have occurred without periods of isolation perhaps in response to differences in local environmental conditions, or alternatively, mtDNA and plumage may have different rates of evolution. Critically, we encountered issues with the placement of the root of the M. splendens complex. The root was placed within the subspecies M. s. splendens separating its northern and southern populations and rendering the subspecies paraphyletic.