The Daily Bulletin Archive

Please join the Biology Department for the seminar "Macrophage NADPH Oxidase Mediates Antifungal Host Defense" by Melissa J. Grimm, Ph.D., from Roswell Park Cancer Institute, on Thursday, April 11, from 12:15 to 1:15 p.m. in Classroom Building B118.

All faculty, staff, and students are welcome. Light refreshments will be served.

Seminar abstract:

Although NADPH oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where NADPH oxidase activity is deemed to be the most critical. In contrast, the role of NADPH oxidase in macrophages is less clear.

To address this question, we evaluated susceptibility to pulmonary aspergillosis in NADPH oxidase-null mice versus transgenic mice with monocyte-targeted NADPH oxidase activity. We found that the lethal inoculum was more than 100-fold greater in transgenic vs. NADPH oxidase-null mice. Consistent with these in vivo results, NADPH oxidase in mouse alveolar macrophages limited germination of phagocytosed Aspergillus fumigatus spores. Also, NADPH oxidase-null mice developed exuberant neutrophilic lung inflammation and pro-inflammatory cytokine responses in response to zymosan, a sterile fungal cell-wall derived product, whereas inflammation in transgenic mice was minimal. Finally, we have also discovered a role for macrophage NADPH oxidase in limiting inflammation by promoting neutrophil death and clearance from the lungs.

Together, our studies show that macrophage NADPH oxidase controls fungal infection and limits acute lung inflammation.