The Journal of infectious diseases
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Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager(-/-)) mice were protected from RSV-induced weight loss and inflammation. ⋯ To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager(-/-) mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager(-/-) mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection.
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There is currently no safe human challenge model of Mycobacterium tuberculosis infection to enable proof-of-concept efficacy evaluation of candidate vaccines against tuberculosis. In vivo antimycobacterial immunity could be assessed using intradermal Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination as a surrogate for M. tuberculosis infection. ⋯ This novel experimental human challenge model provides a platform for the identification of correlates of antimycobacterial immunity and will greatly facilitate the rational down-selection of candidate tuberculosis vaccines. Further evaluation of this model with BCG and new vaccine candidates is warranted.
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Iron restriction has been proposed as a cause of erythropoietic suppression in malarial anemia; however, the role of iron in malaria remains controversial, because it may increase parasitemia. To investigate the role of iron-restricted erythropoiesis, A/J mice were infected with Plasmodium chabaudi AS, treated with intravenous ferric carboxymaltose at different times, and compared with untreated controls. Iron treatment significantly increased weight and hemoglobin nadirs and provided enhanced reticulocytosis and faster recovery, compared with controls. Our findings challenge the restrictive use of iron therapy in malaria and show the need for trials of intravenous ferric carboxymaltose as an adjunctive treatment for severe malarial anemia.