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  • Grimm, Melissa J (author)

Monocyte- and macrophage-targeted NADPH oxidase mediates antifungal host defense and regulation of acute inflammation in mice

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013-04-15
  • The American Association of Immunologists,2013
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-71086
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-71086URI
  • https://doi.org/10.4049/jimmunol.1202800DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:126570467URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Chronic granulomatous disease, an inherited disorder of the NADPH oxidase in which phagocytes are defective in the generation of superoxide anion and downstream reactive oxidant species, is characterized by severe bacterial and fungal infections and excessive inflammation. Although NADPH oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where NADPH oxidase has been deemed vital for pathogen killing. In contrast, the function and importance of NADPH oxidase in macrophages are less clear. Therefore, we evaluated susceptibility to pulmonary aspergillosis in globally NADPH oxidase-deficient mice versus transgenic mice with monocyte/macrophage-targeted NADPH oxidase activity. We found that the lethal inoculum was >100-fold greater in transgenic versus globally NADPH oxidase-deficient mice. Consistent with these in vivo results, NADPH oxidase in mouse alveolar macrophages limited germination of phagocytosed Aspergillus fumigatus spores. Finally, globally NADPH oxidase-deficient mice developed exuberant neutrophilic lung inflammation and proinflammatory cytokine responses to zymosan, a fungal cell wall-derived product composed principally of particulate beta-glucans, whereas inflammation in transgenic and wild-type mice was mild and transient. Taken together, our studies identify a central role for monocyte/macrophage NADPH oxidase in controlling fungal infection and in limiting acute lung inflammation. The Journal of Immunology, 2013, 190: 4175-4184.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Vethanayagam, R Robert (author)
  • Almyroudis, Nikolaos G (author)
  • Dennis, Carly G (author)
  • Khan, A Nazmul H (author)
  • D'Auria, Anthony C (author)
  • Singel, Kelly L (author)
  • Davidson, Bruce A (author)
  • Knight, Paul R (author)
  • Blackwell, Timothy S (author)
  • Hohl, Tobias M (author)
  • Mansour, Michael K (author)
  • Vyas, Jatin M (author)
  • Röhm, MarcUmeå universitet,Klinisk bakteriologi,Molekylär Infektionsmedicin, Sverige (MIMS)(Swepub:umu)maro0101 (author)
  • Urban, Constantin FUmeå universitet,Klinisk bakteriologi,Molekylär Infektionsmedicin, Sverige (MIMS)(Swepub:umu)cour0001 (author)
  • Kelkka, Tiina (author)
  • Holmdahl, RikardKarolinska Institutet (author)
  • Segal, Brahm H (author)
  • Umeå universitetKlinisk bakteriologi (creator_code:org_t)

Related titles

  • In:Journal of Immunology: The American Association of Immunologists190:8, s. 4175-41840022-17671550-6606

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