M-CSF Mediates Host Defense during Bacterial Pneumonia by Promoting the Survival of Lung and Liver Mononuclear Phagocytes.

Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells, and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. M-CSF has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden, and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, proliferation of precursors, or recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and antimicrobial functions of both lung and liver mononuclear phagocytes during pneumonia, and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M-CSF is critical to host defenses against bacterial pneumonia by mediating survival and antimicrobial functions of mononuclear phagocytes in the lungs and liver.

Biology of renal recovery: molecules, mechanisms, and pathways.

Acute kidney injury (AKI) contributes to progressive kidney disease. Although significant advances have been made in the understanding of mechanisms of AKI, less is known about the biological basis that links the initial injury to progressive interstitial fibrosis, tubular dysfunction, and capillary rarefaction. The round table discussion focused on mechanisms of renal recovery and fibrosis following AKI. The knowledge gained by understanding these pathways will serve to identify novel therapeutic targets in the future.

Sources of Support for Studies That Inform Recommendations of the Community Preventive Services Task Force.

OBJECTIVES: The Community Preventive Services Task Force (CPSTF) makes evidence-based recommendations about preventive services, programs, and policies in community settings to improve public health. CPSTF recommendations are based on systematic evidence reviews. This study examined the sponsors (ie, sources of financial, material, or intellectual support) for publications included in systematic reviews used by the CPSTF to make recommendations during a 9-year period. METHODS: We examined systematic evidence reviews (effectiveness reviews and economic reviews) for CPSTF findings issued from January 1, 2010, through December 31, 2018. We assessed study publications used in these reviews for sources of support; we classified sources as government, nonprofit, industry, or no identified support. We also identified country of origin for each sponsor and the most frequently mentioned sponsors. RESULTS: The CPSTF issued findings based on 144 systematic reviews (106 effectiveness reviews and 38 economic reviews). These reviews included 3846 publications: 3363 publications in effectiveness reviews and 483 publications in economic reviews. Government agencies supported 57.1% (n = 1919) of publications in effectiveness reviews and 59.2% (n = 286) in economic reviews. More than 1500 study sponsors from 36 countries provided support. The National Institutes of Health was the leading sponsor for effectiveness reviews (21.3%; 718 of 3363) and economic reviews (16.2%; 78 of 480), followed by the Centers for Disease Control and Prevention (7.0%; 234 of 3363 effectiveness reviews and 14.8%; 71 of 480 economic reviews). CONCLUSIONS: The evidence base used by the CPSTF was supported by an array of sponsors, with government agencies providing the most support. Study findings highlight the need for sponsorship transparency and the role of government as a leading supporter of studies that underpin CPSTF recommendations for improving public health.