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9 results on '"Kruckow, Katherine L."'

2. Chronic TNF exposure induces glucocorticoid‐like immunosuppression in the alveolar macrophages of aged mice that enhances their susceptibility to pneumonia.

Author

Kruckow, Katherine L., Murray, Elizabeth, Shayhidin, Elnur, Rosenberg, Alexander F., Bowdish, Dawn M. E., and Orihuela, Carlos J.

Subjects
*ALVEOLAR macrophages, *TUMOR necrosis factors, *STREPTOCOCCUS pneumoniae, *AGE, *COMMUNITY-acquired pneumonia, *MICE, *MATERNAL age
Abstract

Chronic low‐grade inflammation, particularly elevated tumor necrosis factor (TNF) levels, occurs due to advanced age and is associated with greater susceptibility to infection. One reason for this is age‐dependent macrophage dysfunction (ADMD). Herein, we use the adoptive transfer of alveolar macrophages (AM) from aged mice into the airway of young mice to show that inherent age‐related defects in AM were sufficient to increase the susceptibility to Streptococcus pneumoniae, a Gram‐positive bacterium and the leading cause of community‐acquired pneumonia. MAPK phosphorylation arrays using AM lysates from young and aged wild‐type (WT) and TNF knockout (KO) mice revealed multilevel TNF‐mediated suppression of kinase activity in aged mice. RNAseq analyses of AM validated the suppression of MAPK signaling as a consequence of TNF during aging. Two regulatory phosphatases that suppress MAPK signaling, Dusp1 and Ptprs, were confirmed to be upregulated with age and as a result of TNF exposure both ex vivo and in vitro. Dusp1 is known to be responsible for glucocorticoid‐mediated immune suppression, and dexamethasone treatment increased Dusp1 and Ptprs expression in cells and recapitulated the ADMD phenotype. In young mice, treatment with dexamethasone increased the levels of Dusp1 and Ptprs and their susceptibility to infection. TNF‐neutralizing antibody reduced Dusp1 and Ptprs levels in AM from aged mice and reduced pneumonia severity following bacterial challenge. We conclude that chronic exposure to TNF increases the expression of the glucocorticoid‐associated MAPK signaling suppressors, Dusp1 and Ptprs, which inhibits AM activation and increases susceptibility to bacterial pneumonia in older adults. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Anatomical Site-Specific Carbohydrate Availability Impacts Streptococcus pneumoniae Virulence and Fitness during Colonization and Disease

Author

Im, Hansol, primary, Kruckow, Katherine L., additional, D’Mello, Adonis, additional, Ganaie, Feroze, additional, Martinez, Eriel, additional, Luck, Jennifer N., additional, Cichos, Kyle H., additional, Riegler, Ashleigh N., additional, Song, Xiuhong, additional, Ghanem, Elie, additional, Saad, Jamil S., additional, Nahm, Moon H., additional, Tettelin, Hervé, additional, and Orihuela, Carlos J., additional

Published
2022
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5. Capsule Promotes Intracellular Survival and Vascular Endothelial Cell Translocation during Invasive Pneumococcal Disease

Author

Brissac, Terry, primary, Martínez, Eriel, additional, Kruckow, Katherine L., additional, Riegler, Ashleigh N., additional, Ganaie, Feroze, additional, Im, Hansol, additional, Bakshi, Sayan, additional, Arroyo-Diaz, Nicole M., additional, Spencer, Brady L., additional, Saad, Jamil S., additional, Nahm, Moon H., additional, and Orihuela, Carlos J., additional

Published
2021
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7. Capsule protects against intracellular killing and enables vascular endothelial cell translocation during invasive pneumococcal disease

Author

Brissac, Terry, primary, Martínez, Eriel, additional, Kruckow, Katherine L., additional, Riegler, Ashleigh N., additional, Ganaie, Feroze, additional, Im, Hansol, additional, Bakshi, Sayan, additional, Arroyo-Diaz, Nicole M., additional, Spencer, Brady L., additional, Saad, Jamil S., additional, Nahm, Moon H., additional, and Orihuela, Carlos J., additional

Published
2021
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8. Inhibition of Necroptosis to Prevent Long-term Cardiac Damage During Pneumococcal Pneumonia and Invasive Disease

Author

Beno, Sarah M, primary, Riegler, Ashleigh N, additional, Gilley, Ryan P, additional, Brissac, Terry, additional, Wang, Yong, additional, Kruckow, Katherine L, additional, Jadapalli, Jeevan K, additional, Wright, Griffin M, additional, Shenoy, Anukul T, additional, Stoner, Sara N, additional, Restrepo, Marcos I, additional, Deshane, Jessy S, additional, Halade, Ganesh V, additional, González-Juarbe, Norberto, additional, and Orihuela, Carlos J, additional

Published
2020
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9. Streptococcus pneumoniaeBinds to Host Lactate Dehydrogenase via PspA and PspC To Enhance Virulence

Author

Park, Sang-Sang, Gonzalez-Juarbe, Norberto, Martínez, Eriel, Hale, Joanetha Yvette, Lin, Yi-Han, Huffines, Joshua T., Kruckow, Katherine L., Briles, David E., and Orihuela, Carlos J.

Abstract

Streptococcus pneumoniae(Spn) is the leading cause of community-acquired pneumonia. PspA and PspC are among its most important virulence factors, and these surface proteins carry the proline-rich domain (PRD), whose role was unknown until now.

Published
2021
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