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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Monack, Denise M. Gopinath, Smita Lichtman, Joshua S. Bouley, Donna M. Elias, Joshua E. |
| Description | Author Affiliation: Gopinath S ( Departments of Microbiology and Immunology.); Lichtman JS ( Chemical and Systems Biology.); Bouley DM ( Comparative Medicine, Stanford University School of Medicine, Stanford, CA 94305.); Elias JE ( Chemical and Systems Biology.); Monack DM ( Departments of Microbiology and Immunology, dmonack@stanford.edu.); |
| Abstract | Natural populations show striking heterogeneity in their ability to transmit disease. For example, a minority of infected individuals known as superspreaders carries out the majority of pathogen transmission events. In a mouse model of Salmonella infection, a subset of infected hosts becomes superspreaders, shedding high levels of bacteria (>10(8) cfu per g of feces) but remain asymptomatic with a dampened systemic immune state. Here we show that superspreader hosts remain asymptomatic when they are treated with oral antibiotics. In contrast, nonsuperspreader Salmonella-infected hosts that are treated with oral antibiotics rapidly shed superspreader levels of the pathogen but display signs of morbidity. This morbidity is linked to an increase in inflammatory myeloid cells in the spleen followed by increased production of acute-phase proteins and proinflammatory cytokines. The degree of colonic inflammation is similar in antibiotic-treated superspreader and nonsuperspreader hosts, indicating that the superspreader hosts are tolerant of antibiotic-mediated perturbations in the intestinal tract. Importantly, neutralization of acute-phase proinflammatory cytokines in antibiotic-induced superspreaders suppresses the expansion of inflammatory myeloid cells and reduces morbidity. We describe a unique disease-associated tolerance to oral antibiotics in superspreaders that facilitates continued transmission of the pathogen. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 44 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Anti-Bacterial Agents Pharmacology Drug Resistance, Bacterial Salmonella Infections Transmission Salmonella Typhimurium Pathogenicity Administration, Oral Animals Cytokines Immunology Disease Transmission, Infectious Mice Myeloid Cells Pathology Drug Therapy Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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